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Sample records for prednisolone thalidomide consolidation

  1. Thalidomide-associated thrombocytopenia

    NARCIS (Netherlands)

    Duyvendak, M; Naunton, M.; Kingma, B.J; Brouwers, J.R.B.J.

    2005-01-01

    OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy.

  2. Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis

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    Inayama Yoshiaki

    2010-02-01

    Full Text Available Abstract We report a 14-year-old girl with juvenile dermatomyositis (JDM complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.

  3. Thalidomide and Pregnancy

    Science.gov (United States)

    ... It is recommended that two different and reliable methods of birth control be used if a woman is taking thalidomide. Thalidomide may decrease the effectiveness of oral contraceptives (birth control pills). The manufacturer developed the STEPS ( ...

  4. Thalidomide in dermatology: Revisited

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    Iffat Hassan

    2015-01-01

    Full Text Available The use of thalidomide in relation to dermatology is well- known and enough data is available in the literature about various aspects of thalidomide. Despite being an interesting and useful drug for many dermatoses, it is associated with many health hazards including the birth defects, phocomelia. We hereby present a comprehensive review about thalidomide and its application in dermatology.

  5. Forgive sins: rise of thalidomide

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    Yugandar Inakanti

    2014-04-01

    Full Text Available Thalidomide was originally used as a Wonder Drug to treat morning sickness and insomnia in pregnant women in late 1950s. It became apparent in early 1960s that thalidomide treatment resulted in severe birth defects in thousands of children. Then it was banned in most of countries. Later on discovered anti-inflammatory and anti-angiogenic properties of Thalidomide proved to be useful for treatment of leprosy and multiple myeloma. A series of immunomodulatory drugs created by chemical modification of thalidomide have been developed to overcome the original devastating side effects. It’s being investigated extensively as a treatment for many other severe cutaneous disorders and advanced cancers. We briefly review pharmacological and the therapeutic profile of thalidomide.

  6. [Thalidomide teratogenicity and its direct target identification].

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    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2015-01-01

    Half a century ago, thalidomide was developed as a sedative drug and was wildly used over 40 countries. However the drug has serious birth defects such as amelia and phocomelia. Now thalidomide is regarded as a clinically effective drug and used for the treatment of multiple myeloma under strict controls. The direct target of thalidomide had been a long-standing question. We identified cereblon as a primary direct target protein for thalidomide teratogenicity using new affinity bead technology in 2010. In this review, we introduce an overview of thalidomide teratogenicity, a story about how we identified cereblon, and recent advances in cereblon studies.

  7. Thalidomide increases human keratinocyte migration and proliferation.

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    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  8. Identification of a primary target of thalidomide teratogenicity.

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Suzuki, Takayuki; Ogura, Toshihiko; Hotta, Kentaro; Imamura, Yoshimasa; Yamaguchi, Yuki; Handa, Hiroshi

    2010-03-12

    Half a century ago, thalidomide was widely prescribed to pregnant women as a sedative but was found to be teratogenic, causing multiple birth defects. Today, thalidomide is still used in the treatment of leprosy and multiple myeloma, although how it causes limb malformation and other developmental defects is unknown. Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks. Thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting the associated ubiquitin ligase activity. This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity.

  9. Thalidomide protects mice against LPS-induced shock

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    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  10. Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells.

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    Tachikawa, Saoko; Nishimura, Toshinobu; Nakauchi, Hiromitsu; Ohnuma, Kiyoshi

    2017-10-01

    Thalidomide, which was formerly available commercially to control the symptoms of morning sickness, is a strong teratogen that causes fetal abnormalities. However, the mechanism of thalidomide teratogenicity is not fully understood; thalidomide toxicity is not apparent in rodents, and the use of human embryos is ethically and technically untenable. In this study, we designed an experimental system featuring human-induced pluripotent stem cells (hiPSCs) to investigate the effects of thalidomide. These cells exhibit the same characteristics as those of epiblasts originating from implanted fertilized ova, which give rise to the fetus. Therefore, theoretically, thalidomide exposure during hiPSC differentiation is equivalent to that in the human fetus. We examined the effects of thalidomide on undifferentiated hiPSCs and early-differentiated hiPSCs cultured in media containing bone morphogenetic protein-4, which correspond, respectively, to epiblast (future fetus) and trophoblast (future extra-embryonic tissue). We found that only the number of undifferentiated cells was reduced. In undifferentiated cells, application of thalidomide increased the number of apoptotic and dead cells at day 2 but not day 4. Application of thalidomide did not affect the cell cycle. Furthermore, immunostaining and flow cytometric analysis revealed that thalidomide exposure had no effect on the expression of specific markers of undifferentiated and early trophectodermal differentiated cells. These results suggest that the effect of thalidomide was successfully detected in our experimental system and that thalidomide eliminated a subpopulation of undifferentiated hiPSCs. This study may help to elucidate the mechanisms underlying thalidomide teratogenicity and reveal potential strategies for safely prescribing this drug to pregnant women.

  11. Stability of an extemporaneously prepared thalidomide suspension.

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    Kraft, Shawna; Johnson, Cary E; Tyler, Ryan P

    2012-01-01

    The short-term physical and chemical stability of an oral suspension of thalidomide 20 mg/mL was studied. An oral suspension of thalidomide 20 mg/mL was prepared by emptying the contents of 12 100-mg thalidomide capsules into a glass mortar; 30 mL of Ora-Plus and 30 mL of Ora-Sweet were mixed and added to the thalidomide powder to make a final volume of 60 mL. Three identical samples of the formulation were prepared and placed in 2-oz amber plastic bottles with child-resistant caps and stored under refrigeration (3-5 °C). A 1-mL sample was withdrawn from each of the three samples with a micropipette immediately after preparation and at 7, 14, 21, 28, and 35 days. After further dilution to an expected concentration of 20 μg/mL with acetonitrile-methanol and then dilution with mobile phase, the samples were assayed in duplicate using stability-indicating high-performance liquid chromatography. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point; stability was defined as the retention of at least 90% of the initial concentration of thalidomide. At least 92% of the initial thalidomide concentration remained throughout the 35-day study period. There were no detectable changes in color, odor, or pH and no visible microbial growth in any sample. An extemporaneously prepared suspension of thalidomide 20 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet was stable for at least 35 days when stored in 2-oz amber plastic bottles under refrigeration.

  12. Thalidomide neurotoxicity

    DEFF Research Database (Denmark)

    Clemmensen, O J; Olsen, P Z; Andersen, Klaus Ejner

    1984-01-01

    Of six patients treated with thalidomide for either prurigo nodularis or discoid lupus erythematosus, four had paresthesias in the hands and feet and one also complained of muscular pain and stiffness. Clinical neurological findings in all four patients were normal. Subsequent electrophysiological...

  13. Prednisolone or pentoxifylline for alcoholic hepatitis.

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    Thursz, Mark R; Richardson, Paul; Allison, Michael; Austin, Andrew; Bowers, Megan; Day, Christopher P; Downs, Nichola; Gleeson, Dermot; MacGilchrist, Alastair; Grant, Allister; Hood, Steven; Masson, Steven; McCune, Anne; Mellor, Jane; O'Grady, John; Patch, David; Ratcliffe, Ian; Roderick, Paul; Stanton, Louise; Vergis, Nikhil; Wright, Mark; Ryder, Stephen; Forrest, Ewan H

    2015-04-23

    Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline. A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002). Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone

  14. Defibrotide blunts the prothrombotic effect of thalidomide on endothelial cells.

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    Echart, C L; Somaini, S; Distaso, M; Palumbo, A; Richardson, P G; Fareed, J; Iacobelli, M

    2012-01-01

    Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy has been identified to increase this risk. Defibrotide (DF), a polydisperse oligonucleotide, showed previously to counteract the alterations in endothelial cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis induced by thalidomide. In this in vitro study, MM by itself alters the profibrinolytic potential of ECs decreasing the tissue plasminogen activator (t-PA) and increasing the plasminogen activator inhibitor 1 (PAI-1) levels which is potentiated by thalidomide. Defibrotide was able to counteract these effects. Additionally, DF upregulated the t-PA and downregulated PAI-1 gene expression modulated by thalidomide. Defibrotide also protects ECs from thalidomide-mediated cell death without interfering with its antitumor effects. These findings support DF clinical use for the prevention of DVT induced by immunomodulatory drugs.

  15. Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

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    Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

    2017-01-01

    We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  16. A Novel Green Synthesis of Thalidomide and Analogs

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    Ellis Benjamin

    2017-01-01

    Full Text Available Thalidomide and its derivatives are currently under investigation for their antiangiogenic, immunomodulative, and anticancer properties. Current methods used to synthesize these compounds involve multiple steps and extensive workup procedures. Described herein is an efficient microwave irradiation green synthesis method that allows preparation of thalidomide and its analogs in a one-pot multicomponent synthesis system. The multicomponent synthesis system developed involves an array of cyclic anhydrides, glutamic acid, and ammonium chloride in the presence of catalytic amounts of 4-N,N-dimethylaminopyridine (DMAP to produce thalidomide and structurally related compounds within minutes in good isolated yields.

  17. Pentoxifylline Plus Prednisolone versus Pentoxifylline Only for ...

    African Journals Online (AJOL)

    Background: Prednisolone and pentoxifylline (PTX) have been shown to be individually useful in severe alcoholic hepatitis with Maddrey discriminant function (MDF) score .32. Previous report suggests that PTX is probably superior to prednisolone alone. However the efficacy of PTX and prednisolone combination over PTX ...

  18. Prednisolone Ophthalmic

    Science.gov (United States)

    Poly-Pred® (as a combination product containing Neomycin, Polymyxin B, Prednisolone) ... the following symptom, call your doctor immediately: eye pain If you experience a serious side effect, you ...

  19. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

    Science.gov (United States)

    Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan

    2015-05-01

    Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  20. The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development

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    Rehman, Waqas; Arfons, Lisa M.; Lazarus, Hillard M.

    2011-01-01

    Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses. PMID:23556097

  1. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Hong-xia Xue

    2015-01-01

    Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  2. Thalidomide for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy

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    Geng Song

    2017-03-01

    Full Text Available Background Antiemetic guidelines recommend co-administration of agents to maximize the prevention of chemotherapyinduced nausea and vomiting (CINV, however, the control of delayed CINV is still not satisfactory. The purpose of this study was to evaluate the effectiveness and safety of thalidomide in the prevention of CINV. Methods Of 89 patients enrolled, 83 chemotherapy-naïve patients receiving highly emetogenic chemotherapy (cisplatin 70mg/m2 were randomized into two groups: standard therapy group (ondansetron on day 1, metoclopramide and dexamethasone on days one to five and thalidomide group (in addition to standard emesis prevention, patients received oral 100mg thalidomide on days one to five. Patients recorded nausea and vomiting episodes in a diary. The primary end point was the efficacy of thalidomide in controlling vomiting and nausea on days one to five post cisplatin, and the secondary end point was the safety of the thalidomide. Results No significant differences of complete response rates (no emesis, no use of rescue therapy and no nausea were observed between the two groups, while the percentages of patients with complete response of delayed vomiting on day four and day five were higher in the thalidomide group, furthermore, the complete response rate of delayed nausea for thalidomide group and standard therapy group showed significant differences. Thalidomide group showed a similar safety profile as standard emesis prevention group. Conclusion Addition of thalidomide was generally well tolerated and improved prevention of CINV in patients receiving cisplatinbased chemotherapy to some degree, especially for delayed nausea.

  3. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

    DEFF Research Database (Denmark)

    Zweegman, Sonja; van der Holt, Bronno; Mellqvist, Ulf-Henrik

    2016-01-01

    The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalid......The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone......, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen...... with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS...

  4. Inhibition of DNA synthesis and radiosensitization effects of thalidomide on esophageal carcinoma TE1 cells

    International Nuclear Information System (INIS)

    Yu Jingping; Sun Suping; Sun Zhiqiang; Sun Meiling; Liu Fenju

    2010-01-01

    Objective: To explore the radiosensitization effect of thalidomide combined with X-ray on esophageal carcinoma TE1 cells. Methods: Cell scratch assay was used to detect the inhibition ability of different concentration of Thalidomide on cell invasion and metastasis. H 3 -TdR incorporation assay was used to investigate the inhibition of DNA synthesis in TE1 cells by treated with Thalidomide singly or combination with X-rays. The colony formation assay was used to analyze the radiosensitization of Thalidomide effect on TE1 cells. Results: Thalidomide had obvious inhibition effect on TE1 cell metastasis, DNA synthesis and colony formation, which were correlated with drug concentration. The values D 0 , D q and SF 2 in TE1 cells were gradually decreased with thalidomide concentration increased. When the concentration of thalidomide was 100μg/ml, the SER D 0 and SER D 0 and SER D q were (1.4±0.2) and (1.5±0.1), respectively, While the concentration of thalidomide was 150 μg/ml, the SER D 0 and SER D q were (1.5±0.2) and (1.8±0.2), respectively. Conclusions: Thalidomide could inhibit TE1 cell invasion, metastasis, DNA synthesis, and significantly enhance the radiosensitizing effect on esophageal carcinoma TE1 cells. (authors)

  5. Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century.

    Science.gov (United States)

    Annas, G J; Elias, S

    1999-01-01

    The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters. PMID:9987477

  6. Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century.

    Science.gov (United States)

    Annas, G J; Elias, S

    1999-01-01

    The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters.

  7. Prednisolone multicomponent nanoparticle preparation by aerosol solvent extraction system.

    Science.gov (United States)

    Moribe, Kunikazu; Fukino, Mika; Tozuka, Yuichi; Higashi, Kenjirou; Yamamoto, Keiji

    2009-10-01

    Prednisolone nanoparticles were prepared in the presence of a hydrophilic polymer and a surfactant by the aerosol solvent extraction system (ASES). A ternary mixture of prednisolone, polyethylene glycol (PEG), and sodium dodecyl sulfate (SDS) dissolved in methanol was sprayed through a nozzle into the reaction vessel filled with supercritical carbon dioxide. After the ASES process was repeated, precipitates of the ternary components were obtained by depressurizing the reaction vessel. When a methanolic solution of prednisolone/PEG 4000/SDS at a weight ratio of 1:6:2 was sprayed under the optimized ASES conditions, the mean particle size of prednisolone obtained after dispersing the precipitates in water was observed to be ca. 230 nm. Prednisolone nanoparticles were not obtained by the binary ASES process for prednisolone, in the presence of either PEG or SDS. Furthermore, ternary cryogenic cogrinding, as well as solvent evaporation, was not effective for the preparation of prednisolone nanoparticles. As the ASES process can be conducted under moderate temperature conditions, the ASES process that was applied to the ternary system appeared to be one of the most promising methods for the preparation of drug nanoparticles using the multicomponent system.

  8. Pharmacokinetic-pharmacodynamic modeling of prednisolone-induced lymphocytopenia in man

    NARCIS (Netherlands)

    Oosterhuis, B.; ten Berge, R. J.; Sauerwein, H. P.; Endert, E.; Schellekens, P. T.; van Boxtel, C. J.

    1984-01-01

    The lymphocytopenic effect of prednisolone as quantified by OKT3- and OKT4-positive lymphocyte counts in peripheral blood was studied. Single oral prednisolone doses of 10, 30 and 60 mg, respectively, were given to three groups of five subjects. The time courses of prednisolone concentration and

  9. Antitumorigenic Evaluation of Thalidomide Alone and in Combination with Cisplatin in DBA2/J Mice

    Directory of Open Access Journals (Sweden)

    Jean Marie B. Ruddy

    2002-01-01

    thalidomide failed to inhibit cell proliferation. However, cisplatin treatment with or without thalidomide, significantly inhibited the multiplication of both cell lines in a dose dependent manner. Thalidomide does not appear to be a beneficial adjuvant to cisplatin treatment.

  10. Time to spare newly diagnosed non transplant eligible myeloma (ENDMM) from thalidomide

    DEFF Research Database (Denmark)

    Demarquette, H.; Guidez, S.; Jurczyszyn, A. J.

    2015-01-01

    group, all patients had bortezomib upfront, patients received Vd, VCd or VMP upfront; lenalidomide was then given at first relapse to all patients. The median dose administered of bortezomib was 1.3mg/m2, for a median of 5 cycles (2-9). Results. Overall, the median age was 73 years (range, 65 - 85......), with 35% aged >75. The M/F ratio was 1.1, 38% were ISS 3, the median b2m was 5.5mg/L, 26% had an ECOG score > 2, 42% had renal insufficiency, 11% had elevated LDH, 8% presence of plasmacytoma, and 14% had adverse FISH (del17p, t(4;14) and or t(14;16)). There was no difference in patients' characteristics......,2% were in the thalidomide upfront exposed arm and 53,8% had never been exposed to thalidomide. Patients were required to be aged >65 years, NDMM treated with either thalidomide upfront or never been exposed to thalidomide upfront or later in the myeloma disease course. If not exposed to thalidomide...

  11. Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice.

    Science.gov (United States)

    Payandemehr, Borna; Rahimian, Reza; Gooshe, Maziar; Bahremand, Arash; Gholizadeh, Ramtin; Berijani, Sina; Ahmadi-Dastgerdi, Mohammad; Aminizade, Mehdi; Sarreshte-Dari, Ali; Dianati, Vahid; Amanlou, Massoud; Dehpour, Ahmad Reza

    2014-05-01

    Thalidomide is an old glutamic acid derivative which was initially used as a sedative medication but withdrawn from the market due to the high incidence of teratogenicity. Recently, it has reemerged because of its potential for counteracting number of diseases, including neurodegenerative disorders. Other than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant properties in experimental settings. However, the underlying mechanisms of thalidomide actions are not fully realized yet. Some investigations revealed that thalidomide could elicit immunomodulatory or neuromodulatory properties by affecting different targets, including cytokines (such as TNF α), neurotransmitters, and nitric oxide (NO). In this regard, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of thalidomide is affected through modulation of the l-arginine-nitric oxide pathway or not. Injection of a single effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased the seizure threshold (P<0.05). On the one hand, pretreatment with low and per se noneffective dose of l-arginine [NO precursor] (10, 30 and 60 mg/kg) prevented the anticonvulsant effect of thalidomide. On the other hand, NOS inhibitors [l-NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of thalidomide significantly. In summary, our findings demonstrated that the l-arginine-nitric oxide pathway can be involved in the anticonvulsant properties of thalidomide, and the role of constitutive nNOS is prominent in the reported neuroprotective feature. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, Hui-Ju, E-mail: hjmc@nhri.org.tw [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan (China); Hsu, Chiun [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Chien-Hung [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Chang, Ya-Hui; Chang, Jeffrey S. [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Chen, Li-Tzong [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (China)

    2012-02-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 {+-} 48.9 vs. 148 {+-} 6.2 days, p = .15), or median overall survival (258 {+-} 45.6 vs. 241 {+-} 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-{alpha} levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1

  13. [Current therapeutic indications of thalidomide and lenalidomide].

    Science.gov (United States)

    Ordi-Ros, Josep; Cosiglio, Francisco Javier

    2014-04-22

    Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Behçet syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma. New thalidomide analogues have been developed but lack clinical experience. This paper is a review of the history, pharmacology, mechanism of action, clinical applications and side effects of thalidomide and its analogues. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  14. Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure.

    Science.gov (United States)

    Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

    2015-04-14

    Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. Wild type, inducible nitric oxide synthase (iNOS)(-/-) and endothelial nitric oxide synthase (eNOS)(-/-) mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS(-/-) PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS(-/-) PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS(-/-) or iNOS(-/-) mice. Thalidomide acutely increased plasma NOx in wild type and eNOS(-/-) mice but not iNOS(-/-) mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, e

  15. Follow-up of Thalidomide treatment in patients with Hereditary Haemorrhagic Telangiectasia.

    Science.gov (United States)

    Hosman, A; Westermann, C J J; Snijder, R; Disch, F; Mummery, C L; Mager, J J

    2015-12-01

    Patients with a hereditary vascular disorder called Rendu-Osler-Weber syndrome (Hereditary Haemorrhagic Telangiectasia, HHT) haemorrhage easily due to weak-walled vessels. Haemorrhage in lungs or brain can be fatal but patients suffer most from chronic and prolonged nosebleeds (epistaxis), the frequency and intensity of which increases with age. Several years ago, it was discovered serendipitously that the drug Thalidomide had beneficial effects on the disease symptoms in several of a small group of HHT patients: epistaxis and the incidence of anaemia were reduced and patients required fewer blood transfusions. In addition, they reported a better quality of life. However, Thalidomide has significant negative side effects, including neuropathy and fatigue. We followed up all HHT patients in the Netherlands who had been taking Thalidomide at the time the original study was completed to find out (i) how many had continued taking Thalidomide and for how long (ii) the nature and severity of any side-effects and (iii) whether side-effects had influenced their decision to continue taking Thalidomide. Only a minority of patients had continued taking the drug despite its beneficial effects on their symptoms and that the side effects were the primary reason to stop. Despite symptom reduction, alternative treatments are still necessary for epistaxis in HHT patients and a large-scale clinical trial is not justified although incidental use in the most severely affected patients can be considered.

  16. The Clinical Development of Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer

    National Research Council Canada - National Science Library

    Dlaiani, Danai

    2002-01-01

    ...), assessed by wound healing and peri-operative bleeding; 2) Efficacy of neo-adjuvant thalidomide treatment, as measured by the rate of tumor reduction I PSA decline while on thalidomide therapy; 3...

  17. A Phase II dose titration study of thalidomide for cancer-associated anorexia.

    Science.gov (United States)

    Davis, Mellar; Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Bicanovsky, Leslie; Lagman, Ruth

    2012-01-01

    Sixty-five percent of people with advanced cancer suffers from loss of appetite. Several inflammatory cytokines appear to cause appetite loss in animal models. Thalidomide is an immunomodulatory drug that has been associated with improved appetite in those with HIV infections and cancer. We completed a two-stage Phase II dose titration study of thalidomide, the primary purpose of which was to assess appetite response to thalidomide in cancer-associated anorexia. Individuals older than 18 years of age with active cancer, loss of appetite by numerical rating scale (NRS), life expectancy of at least four weeks, and Eastern Cooperative Oncology Group performance status of 0-3 were entered into the study. Pretreatment screening included medical history, neurologic examination, and symptoms by NRS and categorical scale (CAT). Patients received 50mg of thalidomide by mouth at bedtime for two weeks. Individuals who did not respond were dose escalated to 100mg at night for two weeks. Assessment of appetite, early satiety, fatigue, insomnia, night sweats, pain, and quality of life (QOL) occurred at two-week intervals. Toxicity also was assessed. The primary outcome was appetite response defined as a two-point reduction in the NRS or a one-point improvement in the CAT. Thirty-five patients entered the study; 33 completed 14 days of therapy and were analyzed for efficacy and toxicity. Sixty-four percent who completed at least two weeks of thalidomide had improved appetite. The CAT scores for appetite, insomnia, and QOL improved significantly. The 95% confidence intervals did not overlap. Five participants dropped out because of toxicity: two before two weeks and three later. Thalidomide reduced multiple symptoms commonly associated with cancer-related anorexia and improved QOL. Our findings confirmed and validated a previously published single-arm trial. A recent randomized trial demonstrated greater benefits when thalidomide is used combined with other agents to treat cancer

  18. Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

    Directory of Open Access Journals (Sweden)

    Chunguang Chen

    Full Text Available Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

  19. Alteration of plasma prednisolone levels by indomethacin and naproxen.

    OpenAIRE

    Rae, S A; Williams, I A; English, J; Baylis, E M

    1982-01-01

    Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P less than 0.001) increase in free prednisolone levels after concurrent therapy with either indomethacin or naproxen for 2 weeks. Total prednisolone levels were unchanged. These resu...

  20. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Hulleman, Esther; Kazemier, Karin M.; Holleman, Amy; VanderWeele, David J.; Rudin, Charles M.; Broekhuis, Mathilde J. C.; Evans, William E.; Pieters, Rob; Den Boer, Monique L.

    2009-01-01

    Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant

  1. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Gao, Xiugong; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-01-01

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds

  2. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-08-15

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.

  3. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Ch’ang, Hui-Ju; Hsu, Chiun; Chen, Chien-Hung; Chang, Ya-Hui; Chang, Jeffrey S.; Chen, Li-Tzong

    2012-01-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 ± 48.9 vs. 148 ± 6.2 days, p = .15), or median overall survival (258 ± 45.6 vs. 241 ± 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-α levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT

  4. Thalidomide for Epistaxis in Patients with Hereditary Hemorrhagic Telangiectasia: A Preliminary Study.

    Science.gov (United States)

    Fang, Jia; Chen, Xiaomeng; Zhu, Bijun; Ye, Haibo; Zhang, Weitian; Guan, Jian; Su, Kaiming

    2017-08-01

    To evaluate the effectiveness of thalidomide for epistaxis in hereditary hemorrhagic telangiectasia (HHT), 7 HHT patients with recurrent epistaxis were treated with thalidomide at an initial dose of 50 mg/d, gradually increasing to 100 mg/d if needed. The Epistaxis Severity Score (ESS) was used to evaluate the treatment effects. Patients reported that epistaxis improved 1 to 3 weeks after starting thalidomide. The mean ESS before treatment, at the end of treatment, and 3 months after stopping treatment was 5.03 ± 2.05, 0.90 ± 0.84 ( P = .003), and 1.98 ± 1.33 ( P = .006), respectively. Four patients reported mild to moderate side effects, including drowsiness, dizziness, constipation, nausea, and peripheral neuropathy. Two patients stopped the treatment because of adverse effects. Those results showed that thalidomide may be a treatment choice for recurrent epistaxis in HHT patients, although the side effects should be considered. Further study should focus on guidelines for dosing and course and investigate how to reduce the adverse effects.

  5. The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for Modern Medicine.

    Science.gov (United States)

    Knobloch, J; Jungck, D; Koch, A

    2017-01-01

    Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and antiangiogenic activities are considered in many other refractory diseases. The aim is to develop derivatives that are not teratogenic but maintain the therapeutic potential. This requires detailed knowledge about the underlying molecular mechanisms. Much progress has been made in deciphering the teratogenic mechanisms in the last decade. Here, we summarize these mechanisms, explain thalidomide resistance of rodents, and discuss possible mechanisms that could explain why the drug primarily targets the developing limb in the embryo. We also summarize the most important therapeutic mechanisms. Finally, we discuss which therapeutic and teratogenic mechanisms do and do not overlap, and if there is a chance for the development of non-teratogenic thalidomide derivatives with therapeutic potential. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Thalidomide has a significant effect in patients with thalassemia intermedia.

    Science.gov (United States)

    Li, YunShuan; Ren, Quan; Zhou, Yali; Li, Pingping; Lin, Wanhua; Yin, Xiaolin

    2018-01-01

    To investigate the effect of thalidomide in patients with thalassemia intermedia. We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent. For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1-2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration. Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.

  7. Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

    Science.gov (United States)

    Rodrigues, Gustavo Büchele; Passos, Giselle Fazzioni; Di Giunta, Gabriella; Figueiredo, Cláudia Pinto; Rodrigues, Eduardo Büchele; Grumman, Astor; Medeiros, Rodrigo; Calixto, João B

    2007-03-01

    The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

  8. Systemic effects of chronically administered methyl prednisolonate and methyl 17-deoxyprednisolonate.

    Science.gov (United States)

    Olejniczak, E; Lee, H J

    1984-06-01

    The systemic activities of methyl prednisolonate and methyl 17-deoxyprednisolonate (1) were studied in rats. Methyl 17-deoxyprednisolonate produced significant changes in the amount of sodium ion (decreased) and potassium ion (increased) in urine; however, methyl prednisolonate had no effect on electrolyte balance. Both methyl prednisolonate and methyl 17-deoxyprednisolonate had no effect on liver glycogen content, plasma corticosterone level and relative adrenal weight. In contrast, the parent compound prednisolone caused a significant decrease in liver glycogen content, plasma corticosterone level and relative adrenal weight.

  9. Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

    Science.gov (United States)

    Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

    2009-07-01

    The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

  10. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

    Science.gov (United States)

    Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

    2012-01-05

    Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

  11. Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury

    International Nuclear Information System (INIS)

    Anscher, Mitchell S.; Garst, Jennifer; Marks, Lawrence B.; Larrier, Nicole; Dunphy, Frank; Herndon, James E.; Clough, Robert B.S.; Marino, Christine R.N.; Vujaskovic, Zeljko; Zhou, Sumin; Dewhirst, Mark W.; Shafman, Timothy D.; Crawford, Jeffrey

    2006-01-01

    Purpose: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. Methods and Materials: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status ≥70, and life expectancy ≥6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m 2 ) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. Results: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. Conclusions: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity

  12. Alteration of plasma prednisolone levels by indomethacin and naproxen.

    Science.gov (United States)

    Rae, S A; Williams, I A; English, J; Baylis, E M

    1982-01-01

    Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P less than 0.001) increase in free prednisolone levels after concurrent therapy with either indomethacin or naproxen for 2 weeks. Total prednisolone levels were unchanged. These results could provide an explanation for clinical reports that these two NSAI drugs possess a steroid-sparing effect. PMID:7126420

  13. Magnetic resonance imaging for monitoring the effects of thalidomide on experimental human breast cancers

    International Nuclear Information System (INIS)

    Cyran, Clemens C.; Sennino, Barbara; McDonald, Donald M.; Chaopathomkul, Bundit; Fu, Yanjun; Rogut, Victor S.; Shames, David M.; Wendland, Michael F.; Brasch, Robert C.

    2009-01-01

    Thalidomide, which inhibits angiogenesis in certain tumor types, reduced extravasation of a macromolecular contrast medium (MMCM) in a human breast cancer model as assayed by MMCM-enhanced dynamic magnetic resonance imaging (MRI) and fluorescence microscopy in the same tumors. After a 1-week, three-dose course of thalidomide, the mean MRI-assayed endothelial transfer coefficient, K PS , decreased significantly (p 3 . Correspondingly, microscopic measurements of extravasated MMCM, expressed as fractional area of streptavidin staining, were significantly (p PS values correlated significantly (r 2 =0.55, p<0.05) with microscopic measures of MMCM extravasation. However, no significant differences were observed between saline- and thalidomide-treated tumors with respect to rate of growth, vascular richness, or amount of VEGF-containing cells. Because of its sensitivity to the detection of changes in vascular leakage in tumors, this MMCM-enhanced MRI assay could prove useful for monitoring the effects of thalidomide on an individual patient basis. The significant correlation between MRI and fluorescence microscopic measures of MMCM extravasation supports the utility of the non-invasive MRI approach for assessing the action of thalidomide on tumor blood vessels. (orig.)

  14. Prednisolone and prednisone neo-formation in bovine urine after sampling.

    Science.gov (United States)

    Arioli, F; Casati, A; Fidani, M; Silvestri, M; Pompa, G

    2012-06-01

    The rise in the frequency of detecting prednisolone in bovine urine from northern Italy has come into focus of attention in recent years. The possibility that neo-formation of prednisolone or that prednisone may occur in urine after collection of samples was therefore investigated. Cow urine collected for official routine controls in Lombardy containing more than 80 ng/ml cortisol, and prednisolone and prednisone below the decision limit (CCα) of the method (0.4 and 0.5 ng/ml, respectively) was used. The C1-2 dehydrogenation of naturally present cortisol and cortisone was checked by incubating urine, both contaminated and uncontaminated with faeces, at 37°C and by collecting samples at 0, 1, 2, 4, 6 and 24 h. The influence of Helix pomatia juice was also investigated in order to determine whether deconjugation could influence the reliability of the results. All samples were analysed by HPLC-MS3 for the presence of cortisol, cortisone, prednisolone and prednisone in negative electrospray ionisation mode, utilising the consecutive reaction monitoring of product ions derived from the formate molecular adduct ([M+HCOO]-). The observed neo-formation of prednisolone shows that inappropriate temperatures in sample storage and processing can result in an incorrect accusation of non-compliance. The faecal contamination of urine, performed with the aim to mimic a collection conducted without the necessary care, moreover, evoked a high increase in prednisolone concentration in two out of seven animals. Moreover, H. pomatia juice had no significant effect on the prednisolone concentration, indicating that this corticosteroid is present in its free form in cow urine.

  15. Thalidomide Induces Limb Anomalies by PTEN Stabilization, Akt Suppression, and Stimulation of Caspase-Dependent Cell Death▿

    OpenAIRE

    Knobloch, Jürgen; Schmitz, Ingo; Götz, Katrin; Schulze-Osthoff, Klaus; Rüther, Ulrich

    2007-01-01

    Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalidomide-induced limb truncations result from increased cell death during embryonic limb development and consequential disturbance of limb outgrowth. Here we demonstrate in primary human embryonic cells and in the chicken embryo that thalidomide-induced signaling through bone morphogenetic proteins (...

  16. Plasma and Ocular Prednisolone Disposition after Oral Treatment in Cats

    Directory of Open Access Journals (Sweden)

    María J. Del Sole

    2013-01-01

    Full Text Available Objective. To evaluate the plasma and aqueous humor disposition of prednisolone after oral administration in cats. Methods. Six cats were administered with a single oral dose of prednisolone (10 mg. Blood and aqueous humor samples were serially collected after drug administration. Prednisolone concentrations in plasma and aqueous humor were measured at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, and 5.0 h after administration by a high-performance liquid chromatographic analytical method developed and validated for this purpose. Results. Mean ± standard error (SE of maximum plasma prednisolone concentration (300.8 ± 67.3 ng/mL was reached at 1 h after administration. Prednisolone was distributed to the aqueous humor reaching a mean peak concentration of 100.9 ± 25.5 ng/mL at 1.25 h after administration. The mean ± SE systemic and aqueous humor exposure (AUC was 553.3 ± 120.0 ng*h/mL and 378.8 ± 64.9 ng*h/mL, respectively. A high AUCaqueous humor/AUCplasma ratio was observed (0.68 ± 0.13. The mean half-life time of elimination in plasma and aqueous humor was 0.87 ± 0.16 h and 2.25 ± 0.44 h, respectively. Clinical Significance. The observed high ratio between aqueous humor and plasma prednisolone concentrations indicates that extensive penetration of prednisolone to the anterior segment of the eye may occur. This is the first step that contributes to the optimization of the pharmacological therapeutics for the clinical treatment of uveitis.

  17. Excretion of [3H]prednisolone in clinically normal and experimentally infected bovine udders

    International Nuclear Information System (INIS)

    Geleta, J.N.; Shimoda, W.; Mercer, H.D.

    1984-01-01

    The excretion rate of [3H]prednisolone from clinically normal and experimentally infected udders of 10 lactating cows was studied. Each quarter of 6 cows was injected with a single dose of [3H]prednisolone mixed with non-radioactive prednisolone equivalent to 10 mg in 10 ml of peanut oil base. Each of the remaining 4 cows was given 40 mg of nonradioactive prednisolone and [3H]prednisolone in 60% ethanol IV. Control and postadministration samples of blood, milk, and urine were examined for radioactivity. The effects of [3H]prednisolone were evaluated in the same cows, first in clinically normal udders, then 2 weeks later in udders experimentally infected with Streptococcus agalactiae. Absorption and elimination of prednisolone were the same before and after induced infection. Within 3 hours after intramammary injection, 95% of the labeled prednisolone was absorbed systemically, less than 5% of this dose was recovered in milk, and 29% was excreted in urine. After IV injection of [3H]prednisolone, less than 0.2% of the total radioactivity was recovered in milk and less than 46% was excreted in urine. Clinical mastitis induced by S agalactiae was moderate. Circulating blood leukocytes and somatic cells in the milk of normal cows remained essentially unchanged. The leukocyte response to induced infection was rapid in blood and milk. Large numbers of leukocytes were noticed in the milk and a severe leukopenia occurred. Prednisolone treatment did not alter the number of somatic cells in milk or reduce the inflammatory response of experimentally infected cows

  18. Excretion of (3H)prednisolone in clinically normal and experimentally infected bovine udders

    Energy Technology Data Exchange (ETDEWEB)

    Geleta, J.N.; Shimoda, W.; Mercer, H.D.

    1984-08-01

    The excretion rate of (3H)prednisolone from clinically normal and experimentally infected udders of 10 lactating cows was studied. Each quarter of 6 cows was injected with a single dose of (3H)prednisolone mixed with non-radioactive prednisolone equivalent to 10 mg in 10 ml of peanut oil base. Each of the remaining 4 cows was given 40 mg of nonradioactive prednisolone and (3H)prednisolone in 60% ethanol IV. Control and postadministration samples of blood, milk, and urine were examined for radioactivity. The effects of (3H)prednisolone were evaluated in the same cows, first in clinically normal udders, then 2 weeks later in udders experimentally infected with Streptococcus agalactiae. Absorption and elimination of prednisolone were the same before and after induced infection. Within 3 hours after intramammary injection, 95% of the labeled prednisolone was absorbed systemically, less than 5% of this dose was recovered in milk, and 29% was excreted in urine. After IV injection of (3H)prednisolone, less than 0.2% of the total radioactivity was recovered in milk and less than 46% was excreted in urine. Clinical mastitis induced by S agalactiae was moderate. Circulating blood leukocytes and somatic cells in the milk of normal cows remained essentially unchanged. The leukocyte response to induced infection was rapid in blood and milk. Large numbers of leukocytes were noticed in the milk and a severe leukopenia occurred. Prednisolone treatment did not alter the number of somatic cells in milk or reduce the inflammatory response of experimentally infected cows.

  19. Effects of 5HPP-33,an antiangiogenic thalidomide analog, in mouse whole embryo culture

    Science.gov (United States)

    Thalidomide is a well-known example of a teratogen which has been shown to have an inhibitory effect on angiogenesis. As a result of its targeted effect on immature blood vessels, anti-angiogenic specific chemical analogs were developed to maximize this mechanism of thalidomide e...

  20. Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial

    Directory of Open Access Journals (Sweden)

    Wang Kangjun

    2011-06-01

    Full Text Available Abstract Background There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. Methods/Design In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1 placebo prednisolone group, 2 prednisolone group, 3 placebo prednisolone plus acute stage acupuncture group, 4 prednisolone plus acute stage acupuncture group, 5 placebo prednisolone plus resting stage acupuncture group, 6 prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain, the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. Discussion The result of this trial will assess the

  1. Treatment of Hepatic Epithelioid Hemangioendothelioma: Finding Uses for Thalidomide in a New Era of Medicine

    Directory of Open Access Journals (Sweden)

    Matthew P. Soape

    2015-01-01

    Full Text Available Hepatic epithelioid hemangioendothelioma (HEH is extremely rare, occurring in 1 to 2 per 100,000, with chemotherapy options not well defined. Our case involved a 49-year-old female who had hepatic masses and metastasis to the lungs with a liver biopsy revealing HEH. After developing a rash from sorafenib, thalidomide was started with the progression of disease stabilized. Resection is only an option in 10% of the cases; therefore, chemotherapy is the only line of treatment. Newer chemotherapy alternatives are targeting angiogenesis via the vascular endothelial growth factor. Thalidomide was first used as an antiemetic, but, sadly, soon linked to phocomelia birth defects. Given the mechanism of action against angiogenesis, thalidomide has a valid role in vascular tumors. In conclusion, the use of thalidomide as chemotherapy is novel and promising, especially in the setting of a rare vascular liver tumor such as HEH.

  2. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation

    Science.gov (United States)

    Davies, Faith E.; Gregory, Walter M.; Russell, Nigel H.; Bell, Sue E.; Szubert, Alexander J.; Coy, Nuria Navarro; Cook, Gordon; Feyler, Sylvia; Byrne, Jenny L.; Roddie, Huw; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Jackson, Graham H.; Child, J. Anthony

    2011-01-01

    As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111. PMID:21652683

  3. Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Michelle S. Boyar

    2008-01-01

    Full Text Available We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m2/day for 7 days every other week was administered with concomitant thalidomide (200 mg/day, and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10% partial responses. Five patients (24% had stable disease for at least six months. Fourteen patients (67% progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients was 9.5 months [95% CI 7–28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

  4. Effect of systemic clarithromycin and prednisolone on histamine-induced otitis media in guinea pigs.

    Science.gov (United States)

    Kozan, Günay; Aktan, Bülent; Sakat, Muhammed Sedat; Kurt, Sezgin; Öner, Fatih; Kara, Adem

    2015-01-01

    The results of the study showed that clarithromycin has anti-inflammatory and antioxidant effects and, when it is combined with prednisolone, those effects gain strength. The present study aims to investigate the effects that the antioxidant and anti-inflammatory activities of clarithromycin and/or prednisolone have on experimental otitis media in effusion-induced guinea-pigs. In this study, 35-male guinea pigs were randomly divided into five-groups. For the experimental otitis media, intra-tympanic histamine (0.1 ml) was injected into the guinea pigs in all of the groups except the control group. Then, 24-h after the intra-tympanic injections, clarithromycin (15 mg/kg/day) and/or prednisolone (1 mg/kg/day) were applied intraperitoneally to the guinea-pigs for 7-days. The biochemical analysis showed an increase in antioxidant capacity and a decrease in oxidant status and malondialdehyde (MDA) levels in the clarithromycin group and the prednisolone group and especially in the clarithromycin+prednisolone group, as compared to the experimental group (p < 0.05). In the cytokine analysis, lower levels of interleukin (IL)-6 and IL-17A and higher IL-10 were found in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups than in the experimental group (p < 0.05). Furthermore, the histologic analyses showed histopathologic changes in the middle ear mucosa of the experimental group, but comparatively fewer-histopathologic changes were observed in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups.

  5. Elucidation of the pharmacokinetics of prednisone and prednisolone: elimination and the effect of estrogen

    International Nuclear Information System (INIS)

    Gustavson, L.E.

    1985-01-01

    Several aspects of the pharmacokinetics of the interconvertible glucocorticoids prednisone and prednisolone have been studied. The pharmacokinetics of prednisolone were examined in postmenopausal women taking conjugated estrogens and age-matched control women. The subjects received iv bolus doses of 0.14 and 0.55 mg/kg prednisolone. Expected increases in clearance and volume of distribution with increasing dose were observed for total prednisolone in all subjects. At both doses, significant decreases in total and unbound prednisolone clearance were observed in the women taking estrogen compared to the controls. Volume of distribution was unchanged. The decreases in clearance are smaller than those observed in young women taking oral contraceptives indicating that factors other than estrogen administration may influence prednisolone clearance in oral contraceptive users. While the protein binding of prednisolone is well characterized, little is known about the protein binding of prednisone. Equilibrium dialysis employing [ 3 H]prednisone was used to study the binding of prednisone in human plasma containing endogenous hydrocortisone. Plasma was obtained from volunteers with normal and elevated transcortin binding capacities (CAP/sub T/). Prednisolone binding exhibits marked concentration dependence and sensitivity to CAP/sub T/. In contrast, prednisone binding is independent of concentration and CAP/sub T/

  6. A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide

    Directory of Open Access Journals (Sweden)

    Paiva Renata T

    2012-06-01

    Full Text Available Abstract Background Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. Results We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. Conclusions The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

  7. Resolving a double standard for risk management of thalidomide: an evaluation of two different risk management programmes in Japan.

    Science.gov (United States)

    Ooba, Nobuhiro; Sato, Tsugumichi; Watanabe, Hikaru; Kubota, Kiyoshi

    2010-01-01

    Thalidomide, once withdrawn because of its teratogenicity, has now been re-launched worldwide. In Japan, thalidomide has been imported by individual doctors since around the year 2000. In October 2008, it was approved for the treatment of multiple myeloma (MM) by the Ministry of Health, Labour and Welfare (MHLW) on the condition that the manufacturer implemented a risk management programme termed the Thalidomide Education and Risk Management System (TERMS). It is likely that the imports of thalidomide will be used off-label to treat diseases other than MM. Thus, the MHLW is also planning to introduce a web-based registration system, referred to as the Safety Management System for Unapproved Drugs (SMUD), for thalidomide imported by individual doctors. To evaluate the difference between TERMS and SMUD and establish a way to resolve the 'double standard' for risk management of thalidomide treatment in Japan. The fraction of patients with disorders other than MM was estimated by the volume of annual imports obtained from the MHLW and records of the imports for patients with MM, other oncological diseases (ODs) and non-ODs in 2007 through a major supplier covering 63% of the total imported thalidomide. The information for TERMS was obtained from web pages of the manufacturer and the MHLW. The components of TERMS were compared with those in SMUD. Provided that the distribution of the indication for thalidomide (MM) in 2007, estimated from the records of imports through the major supplier, is representative of the entire nation, it is estimated that on average 866 patients, including 851 (98.3%) with MM, are using thalidomide on any one day. However, if the major supplier's imports, which account for 63% of the total imports, are not representative of the nation as a whole, possibly only half of the patients treated with thalidomide in Japan have MM. This would be the case in a scenario where the remaining 37% of imports are exclusively used to treat disorders other than

  8. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    International Nuclear Information System (INIS)

    Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-01-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects

  9. Prednisolone reduces nitric oxide-induced migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, P; Daugaard, D; Lassen, L H

    2009-01-01

    BACKGROUND AND PURPOSE: Glyceryl trinitrate (GTN) induces delayed migraine attacks in migraine patients. The purpose of this study was to investigate whether pre-treatment with prednisolon could decrease this effect of GTN. METHODS: In this double-blind, randomized and placebo-controlled, crossover...... study 15 migraineurs with migraine without aura were pre-treated with 150 mg of prednisolone or placebo followed by a 20-min infusion of GTN (0.5 ug/kg/min). One hour after the GTN-infusion, the participants were sent home, but continued to rate headache and possible associated symptoms by filling out...... a headache diary every hour for 12 h. There were two equal primary efficacy end-points: frequency of delayed migraine and intensity of delayed headache. RESULTS: Nine patients experienced a GTN headache fulfilling the diagnostic criteria for migraine without aura on the placebo day compared with four...

  10. Emerging role of thalidomide in the treatment of gastrointestinal bleeding.

    Science.gov (United States)

    McFarlane, Michael; O'Flynn, Lauren; Ventre, Rachel; Disney, Benjamin R

    2018-04-01

    Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

  11. Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hsu, Wei-Chung; Chung, Na-Na; Wang, Po-Ming; Ying, Kung-Shih; Shin, Jeng-Shiann; Chao, Che-Jen; Lin, Gau-De; Chan, Sue-Ching; Ting, Lai-Lei

    2006-01-01

    The purpose of this study was to evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. Between 1999 and 2003, 121 patients (mean age, 54.4±12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52±408.50 cm 3 (range, 26.89-2284.82 cm 3 ). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. Treatment responses were observed in 61% of the patients. Liver cirrhosis (P=0.001) and tumor size (P=0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P=0.003), Karnofsky performance status (P=0.007), tumor size (P<0.001), portal vein tumor thrombosis (P<0.001) and alpha-fetoprotein level (P=0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P=0.039) and alpha-fetoprotein level (P=0.006) were shown to be factors affecting survival. Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma. (author)

  12. Elotuzumab in combination with thalidomide and low-dose dexamethasone

    DEFF Research Database (Denmark)

    Mateos, Maria-Victoria; Granell, Miguel; Oriol, Albert

    2016-01-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-...

  13. Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

    Science.gov (United States)

    Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

    2007-12-01

    Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

  14. Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ping He

    Full Text Available Thalidomide is a tumor necrosis factor alpha (TNFα inhibitor which has been found to have abilities against tumor growth, angiogenesis and inflammation. Recently, it has been applied in clinic for the treatment of multiple myeloma as well as some inflammatory diseases. However, whether thalidomide has any therapeutic effects on neurodegenerative disorders, i.e. Alzheimer's disease (AD is not clear. AD is characterized by excessive amount of amyloid β peptides (Aβ, which results in a significant release of inflammatory factors, including TNFα in the brain. Studies have shown that inhibition of TNFα reduces amyloid-associated pathology, prevents neuron loss and improves cognition. Our recent report showed that genetic inhibition of TNFα/TNF receptor signal transduction down-regulates β amyloid cleavage enzyme 1 (BACE1 activity, reduces Aβ generation and improves learning and memory deficits. However, the mechanism of thalidomide involving in the mitigation of AD neuropathological features remains unclear. Here, we chronically administrated thalidomide on human APPswedish mutation transgenic (APP23 mice from 9 months old (an onset of Aβ deposits and early stage of AD-like changes to 12 months old. We found that, in addition of dramatic decrease in the activation of both astrocytes and microglia, thalidomide significantly reduces Aβ load and plaque formation. Furthermore, we found a significant decrease in BACE1 level and activity with long-term thalidomide application. Interestingly, these findings cannot be observed in the brains of 12-month-old APP23 mice with short-term treatment of thalidomide (3 days. These results suggest that chronic thalidomide administration is an alternative approach for AD prevention and therapeutics.

  15. Safety of thalidomide in newly diagnosed elderly myeloma patients

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Waage, Anders; Hulin, Cyrille

    2013-01-01

    Background. Melphalan-prednisone-thalidomide (MPT) improves outcome in multiple myeloma (MM) patients, and it is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. Design and Methods. An individual patient data...

  16. Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide?

    DEFF Research Database (Denmark)

    Beksac, Meral; Waage, Anders; Bringhen, Sara

    2015-01-01

    of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP...... ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor...

  17. Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

    Directory of Open Access Journals (Sweden)

    T.B.M. Castro

    2016-01-01

    Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

  18. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

    Science.gov (United States)

    Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

    2012-01-01

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior

  19. Pyoderma Gangranosum of the Penis

    Science.gov (United States)

    Kim, Tae Heung; Oh, Seung Young

    2009-01-01

    We report a patient who developed pyoderma gangrenosum in the penis with invasion of the distal urethra. The patient was treated with prednisolone and thalidomide, followed by a reconstructive surgical repair using a scrotal island flap. We report this case with a brief review of the literature. PMID:19949683

  20. Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

    Directory of Open Access Journals (Sweden)

    A.M. Sales

    2007-02-01

    Full Text Available Type II reaction in leprosy, or erythema nodosum leprosum (ENL, is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

  1. Mullerian agenesis associated with in-utero thalidomide exposure: A case report

    Directory of Open Access Journals (Sweden)

    Sarah Dotters-Katz

    2013-09-01

    Full Text Available Thalidomide is a well-known teratogen, which is experiencing resurgence as new uses are identified. Exposure is classically associated with limb deformities, such as: dysmelia, phocomelia, preaxial hypoplasia and polydactyly, in addition to visceral anomalies that have been documented as well. We report a case of a 38 year-old nulligravid female, who was previously evaluated for primary amenorrhea, and given the presumptive false diagnosis of an imperforate hymen. On magnetic resonance imaging (MRI exam, she was noted to have uterovaginal agenesis. The implications of thalidomide on women’s health extend beyond external birth defects. Although, most commonly associated with limb deformities, there may also be gynecologic implications of in utero exposure. As this medication is increasingly used for various medical conditions, obstetricians/gynecologists need to remain aware of this potential mullerian teratogenic effect.

  2. Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats.

    Science.gov (United States)

    Kuncha, Madhusudana; Naidu, Vegi Ganga Modi; Sahu, Bidya Dhar; Gadepalli, Shankar Ganesh; Sistla, Ramakrishna

    2014-01-01

    The present study was aimed at investigating the effect of curcumin in combination with prednisolone for the effective treatment of arthritis with reduced side effects when glucocorticoids therapy is indicated. Arthritis was induced in wistar rats by subplantar injection of Freund's complete adjuvant, and animals were observed for the symptoms of arthritis during the period of 21 days. Combined treatment of curcumin with various doses of prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the efficacy and toxicity induced by steroid. Arthritic animals showed significant increase in tumour necrosis factor-α and IL-1β levels in paw tissue and IL-1β in serum. Combined therapy of curcumin with low doses of prednisolone showed pronounced beneficial effect on joint swelling, leucocyte count and biochemical parameters compared with prednisolone groups. Among the different doses used in the study, prednisolone at 1.25 mg/kg in combination with curcumin showed beneficial anti-arthritic activity and also reduced the steroid toxicity. This is evidenced by increase in body weight, low toxicity to immune organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and potent inhibition of cytokines in combination group. Therefore, combined treatment of curcumin with low doses of prednisolone may find therapeutic use in arthritis. © 2013 Royal Pharmaceutical Society.

  3. HPLC determination of betamethasone and prednisolone in urine samples using monolithic column

    International Nuclear Information System (INIS)

    Abro, K.; Memon, N.; Bhanger, M.I.

    2011-01-01

    A fast and reliable HPLC method is reported for the separation and quantification of betamethasone and prednisolone in urine samples using Chromolith at the rate of Performance RP-l8e (100 mm x 4.6 mm) column. The separation and detection was achieved using an isocratic mobile phase composed of methanol:water (44:56 v/v) at 2.0 mL/min and wavelength of 254 nm. After successful optimisation of method parameters, it was applied to the urine samples. Solid phase extraction technique was used to clean the sample before analysis. The developed method was validated for the system suitability, precision and accuracy. The limits of defection for the prednisolone and betamethasone are 0.11 ng and 0.075 ng/10 macro L injection, respectively allowing their determination in human urine samples. Recovery for spiked urine samples was in the range of 97-103 %. The method offers a valuable alternative to the methodologies currently employed for separation and quantification of prednisolone and betamethasone in urine samples. A fast and reliable HPLC method is reported for the separation and quantification of betamethasone and prednisolone in urine samples using Chromolith at the rate of Performance RP-l8e (100 mm x 4.6 mm) column. The separation and detection was achieved using an isocratic mobile phase composed of methanol:water (44:56 v/v) at 2.0 mL/min and wavelength of 254 nm. After successful optimisation of method parameters, it was applied to the urine samples. Solid phase extraction technique was used to clean the sample before analysis. The developed method was validated for the system suitability, precision and accuracy. The limits of defection for the prednisolone and betamethasone are 0.11 ng and 0.075 ng/10 macro L injection, respectively allowing their determination in human urine samples. Recovery for spiked urine samples was in the range of 97-103 %. The method offers a valuable alternative to the methodologies currently employed for separation and quantification

  4. Thalidomide for control delayed vomiting in cancer patients receiving chemotherapy

    International Nuclear Information System (INIS)

    Han, Z.; Sun, X.; Du, X.

    2016-01-01

    To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Study Design: Randomized, double-blind controlled study. Place and Duration of Study: The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. Methodology: A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the ?2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). Results: The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (?2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Conclusion: Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

  5. Pentoxifylline Plus Prednisolone versus Pentoxifylline Only for ...

    African Journals Online (AJOL)

    few days. Oral thrush, impaired glucose tolerance, poor wound healing were some of the significant problems faced by the patients in the PTX plus prednisolone group. Retrospectively, on analyzing different liver function scores at the time of inclusion, higher MDF, MELD, GASH, Child-Pugh. Table 2: Morbidity/complications ...

  6. Studies on Dissolution Enhancement of Prednisolone, a Poorly Water-Soluble Drug by Solid Dispersion Technique

    Directory of Open Access Journals (Sweden)

    Parvin Zakeri-Milani

    2011-06-01

    Full Text Available Introduction: Prednisolone is a class II substance according to the Biopharmaceutics Classification System. It is a poorly water soluble agent. The aim of the present study was to improve dissolution rate of a poorly water-soluble drug, prednisolone, by a solid dispersion technique. Methods: Solid dispersion of prednisolone was prepared with PEG 6000 or different carbohydrates such as lactose and dextrin with various ratios of the drug to carrier i.e., 1:10, 1:20 and 1:40. Solid dispersions were prepared by coevaporation method. The evaluation of the properties of the dispersions was performed using dissolution studies, Fourier-transform infrared spectroscopy and x-ray powder diffractometery. Results: The results indicated that lactose is suitable carriers to enhance the in vitro dissolution rate of prednisolone. The data from the x-ray diffraction showed that the drug was still detectable in its solid state in all solid dispersions except solid dispersions prepared by dextrin as carrier. The results from infrared spectroscopy showed no well-defined drug–carrier interactions for coevaporates. Conclusion: Solid dispersion of a poorly water-soluble drug, prednisolone may alleviate the problems of delayed and inconsistent rate of dissolution of the drug.

  7. Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo.

    Science.gov (United States)

    Vasvari, Gergely P; Dyckhoff, Gerhard; Kashfi, Farzaneh; Lemke, Britt; Lohr, Jennifer; Helmke, Burkhard M; Schirrmacher, Volker; Plinkert, Peter K; Beckhove, Philipp; Herold-Mende, Christel C

    2007-10-15

    Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro, and which tumor-derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low-dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro. Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor-cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il-8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide-mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. (c) 2007 Wiley-Liss, Inc.

  8. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials

    DEFF Research Database (Denmark)

    Fayers, Peter M; Palumbo, Antonio; Hulin, Cyrille

    2011-01-01

    or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS...

  9. Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling.

    Science.gov (United States)

    Sun, Xiang; Xu, Yang; Wang, Yi; Chen, Qian; Liu, Liu; Bao, Yangyi

    2018-05-15

    BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC. MATERIAL AND METHODS Humanized NSCLC cell lines PC9 and A549 were co-cultured with thalidomide and/or icotinib to test for anti-tumor efficiency. Cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry and cell migration by wound healing assay. Western blot was performed to determine the expression of caspase-3, -8, -9, Bax, EGFR, VEGF-R, AKT, ERK, MMP2, MMP9, and NF-κB. The xenograft mouse model was used to explore the effects of thalidomide and icotinib in vivo. Immunohistochemical testing was used to determine the expression of Ki-67 and TUNEL staining in tumor tissues. RESULTS Treatments of thalidomide and/or icotinib reduced cell viability, induced apoptosis, and suppressed migration. Attenuation of pEGFR and pVEGF-R resulted in deactivation of ERK and AKT pathways, which eventually increased the anti-proliferative response. In PC9 xenograft model, combined administration of thalidomide and icotinib restrained tumor growth with remarkable reduced Ki-67 index and increased TUNEL positive cells. CONCLUSIONS Thalidomide sensitizes icotinib to increase apoptosis and prevent migration, and it may be a potentially promising anti-tumor drug in lung cancer multi-modality therapy.

  10. Greater therapeutic efficacy of prednisolone plus medicinal herbs than prednisolone or medicinal herbs alone in patients with oral lichen planus

    Directory of Open Access Journals (Sweden)

    Chang-Ta Chiu

    2010-12-01

    Conclusion: Our results suggest that treatment consisting of prednisolone plus traditional medicinal herbs can improve OLP symptoms, relieve pain, reduce recurrent severity, and increase the disease-free period. The benefits of combined therapy for OLP should be investigated by conducting a prospective randomized clinical trial in the future.

  11. Comparative analysis of different brands of prednisolone tablets ...

    African Journals Online (AJOL)

    The experiment involves analysis of nine brands of prednisolone, using ultra violet spectrophotometer in the range of (200-400nm) and high performance liquid chromatography (HPLC) in which the samples were dissolved in various solvents and their various absorbance, peak area at various wavelength were determined ...

  12. Significance of Fractionated Administration of Thalidomide Combined With γ-Ray Irradiation in Terms of Local Tumor Response and Lung Metastasis

    Science.gov (United States)

    Masunaga, Shin-ichiro; Sanada, Yu; Moriwaki, Takahiro; Tano, Keizo; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Watanabe, Tsubasa; Nakagawa, Yosuke; Maruhashi, Akira; Ono, Koji

    2014-01-01

    Background The aim of this study was to evaluate the significance of fractionated administration of thalidomide combined with γ-ray irradiation in terms of local tumor response and lung metastatic potential, referring to the response of intratumor quiescent (Q) cells. Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumor-bearing mice then received γ-ray irradiation after thalidomide treatment through a single or two consecutive daily intraperitoneal administrations up to a total dose of 400 mg/kg in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results Thalidomide raised the sensitivity of the total cell population more remarkably than Q cells in both single and daily administrations. Daily administration of thalidomide elevated the sensitivity of both the total and Q cell populations, but especially the total cell population, compared with single administration. Daily administration, especially combined with MTH, decreased the number of lung metastases. Conclusion Daily fractionated administration of thalidomide in combination with γ-ray irradiation was thought to be more promising than single administration because of its potential to enhance local tumor response and repress lung metastatic potential. PMID:29147396

  13. Use of a combination of prednisolone and rosuvastatin for treatment of a pyogranuloma in a dog.

    Science.gov (United States)

    Yuki, Masashi; Hirano, Takashi

    2010-04-01

    A 6-year-old spayed female Miniature Dachshund was examined because of a 3-day history of anorexia and diarrhea. A lump was detected during abdominal palpation. Biochemical abnormalities included increases in serum concentrations of total protein, globulin, and C-reactive protein (CRP). Abdominal radiography and abdominal ultrasonography revealed a mass on the caudal aspect of the right kidney. Exploratory laparotomy confimed the mass; however, it could not be excised because it was strongly adhered to surrounding tissues. Histologic examination of a tissue sample from the mass led to a diagnosis of pyogranuloma. The dog was treated with rosuvastatin, but no improvement was evident. Administration of a high dose of prednisolone (1 mg/kg [0.45 mg/lb], PO, q 12 h) was initiated. The CRP concentration returned to within reference limits, and the mass gradually decreased in size. The prednisolone dosage was tapered to 0.14 mg/kg (0.064 mg/lb), PO, every 12 hours. However, once the low dosage of prednisolone was reached, CRP concentration and size of the mass increased. Rosuvastatin was subsequently combined with the low dosage of prednisolone. After 1 week of the combination treatment, the CRP concentration returned to within reference limits, and the mass was reduced in size. The mass eventually could not be detected ultrasonographically. A low dose of prednisolone was not effective against the pyogranuloma. However, administration of a low dose of prednisolone in combination with rosuvastatin caused decreases in CRP concentration and size of the pyogranuloma. Thus, statins may act as immunosuppressants.

  14. Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

    Directory of Open Access Journals (Sweden)

    Seyed Amir Dadkhahi

    2017-05-01

    Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

  15. Adrenal insufficiency is seen in more than one-third of patients during ongoing low-dose prednisolone treatment for rheumatoid arthritis

    DEFF Research Database (Denmark)

    Borresen, Stina Willemoes; Klose, Marianne; Baslund, Bo

    2017-01-01

    /day) prednisolone treatment, a dose by itself too low to cover glucocorticoid needs during stress. Design and methods: Cross-sectional study in 42 patients with rheumatoid arthritis (29 women, aged 36-86 years) treated with 5 mg prednisolone/day, who had received prednisolone for ≥6 months (median: 66, range: 6...

  16. [Antagonistic action of prednisolone and buformin in the carbohydrate metabolism of healthy persons (author's transl)].

    Science.gov (United States)

    Bottermann, P; Schweigart, U; Ermler, R

    1976-02-13

    Intravenous glucose tolerance tests were performed and changes of blood glucose and insulin concentration were measured to examine whether the diabetogenic effect of glucocorticoides can be compensated by biguanides. Seven standard weight volunteers with a healthy metabolism were given prednisolone and buformin as well as a combination of both. In spite of the reactively higher insulin secretion after treatment with prednisolone the glucose tolerance was reduced. In contrast, treatment with biguanide improved the glucose tolerance while decreasing the insulin secretion. It was nearly possible to compensate the negative effect of prednisolone on the carbohydrate metabolism by biguanides. We, therefore, consider a preventive administration of biguanides to be effective in long term or high dosage administration of glucocorticoides.

  17. A double blind controlled trial of prednisolone-21-phosphate suppositories in the treatment of idiopathic proctitis

    Science.gov (United States)

    Lennard-Jones, J. E.; Baron, J. H.; Connell, A. M.; Jones, F. Avery

    1962-01-01

    A double blind trial of prednisolone suppositories in out-patients with idiopathic proctitis is reported. Significant improvement was noted. When prednisolone suppositories were given after the patient had already used suppositories of base alone for three weeks the active treatment was no longer so effective. PMID:13929632

  18. Synthesis and evaluation of 4-[F-18]fluoro thalidomide for the in vivo studies of angiogenesis

    International Nuclear Information System (INIS)

    Kim, D. H.; Choi, Y. S.; Jeong, K. H.; Lee, K. H.; Choi, Y.; Kim, B. T.

    2005-01-01

    Thalidomide has been recently rediscovered for its possible utility as an antitumor agent, although it was marketed as a sedative in the 1950s and later found to be a potent teratogen. In this study, therefore, F-18 labeled thalidomide was synthesized and evaluated for the in vivo studies of angiogenesis. 4-[F-18]Fluoro thalidomide ([F-18]1) was prepared by labeling of 4-trimethylammonium thalidomide triflate with TBA[F-18]F in DMSO (90 .deg. C, 10 min) and purified by HPLC. The triflate salt was prepared from 3-fluoro phthalic anhydride in 3 steps. [F-18]1 was incubated with HUVEC cells at 37 .deg. C for 15, 30, 60, and 120 min, respectively. Dynamic PET images of [F-18]1 was obtained in mice implanted with LLC cells. In vitro metabolism study of [F-18]1 was carried out using mouse, rabbit, or human liver microsomes in the presence of NADPH, and the metabolites obtained from the mouse liver microsomal incubation of 1 were analyzed using LC-MS. Radiochemical yield of [F-18]1 was 50-60%, and the specific activity was 42-120 GBq/imol. The HUVEC cell uptake of [F-18]1 increased with time (100% at 15 min and 241% at 120 min). PET images showed that the radioactivity was accumulated in the liver, the kidneys and the bladder of the mice, and brain uptake was shown from 40 min postinjection. However, there was low level of radioactivity uptake in tumor. [F-18]1 was not metabolized by mouse, rabbit, or human liver microsomes but was hydrolyzed significantly at physiological pH. The hydrolyzed product was further analyzed by LC-MS, showing a mass peak corresponding to that of 4-fluoro-N-(o-carboxybenzoyl)glutamic acid imide. This result suggests that [F-18]1 is easily hydrolyzed at physiological pH and thus may not be suitable for the in vivo studies of tumor angiogenesis at least in rodents, although it was reported that the hydrolysis product of thalidomide may be responsible for its angiogenesis activity in humans

  19. Bioavailability of prednisolone in rabbits: Comparison of a highviscosity gel and an aqueous suspension - single- and repeated applications

    DEFF Research Database (Denmark)

    Johansen, Sven; Rask-Pedersen, Eva; Prause, J.U.

    1994-01-01

    Øjenpatologi, carbomer, vehicle, fusidic acid, ophthalmic bioavailability, rabbit, aqueous suspension, prednisolone acetate, sulfacetamide sodium......Øjenpatologi, carbomer, vehicle, fusidic acid, ophthalmic bioavailability, rabbit, aqueous suspension, prednisolone acetate, sulfacetamide sodium...

  20. Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma.

    Science.gov (United States)

    Mark, Tomer M; Bowman, Isaac A; Rossi, Adriana C; Shah, Manan; Rodriguez, Melissa; Quinn, Ryann; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Jayabalan, David; Ely, Scott; Coleman, Morton; Chen-Kiang, Selina; Niesvizky, Ruben

    2014-12-01

    We studied T-BiRD (thalidomide [Thalomid(®)], clarithromycin [Biaxin(®)], lenalidomide [Revlimid(®)] and dexamethasone) in symptomatic, newly diagnosed multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide 25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11 patients who underwent autologous stem cell transplantation as part of first-line therapy. The 4-year overall survival rate was 74.9%, and the median progression-free survival was 35.6 months. Eight patients discontinued due to regimen toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD is a highly active regimen with potential toxicity limitations. ClinicalTrials.gov identifier: NCT00538733.

  1. A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects

    DEFF Research Database (Denmark)

    Hansen, M; Podenphant, J; Florescu, A

    1999-01-01

    OBJECTIVES: To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis. METHODS: One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti......-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters......, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation. RESULTS: The results showed that disease activity in the prednisolone treated group was reduced...

  2. 21 CFR 522.1881 - Sterile prednisolone acetate aqueous suspension.

    Science.gov (United States)

    2010-04-01

    ... and for various stress conditions when corticosteroids are required while the animal is being treated... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1881 Sterile prednisolone acetate aqueous suspension. (a) Specifications. Each...

  3. 75 FR 4692 - Ophthalmic and Topical Dosage Form New Animal Drugs; Miconazole, Polymixin B, and Prednisolone...

    Science.gov (United States)

    2010-01-29

    ... nitrate, polymixin B sulfate, and prednisolone acetate for the treatment of otitis externa in dogs. DATES... SUROLAN (miconazole nitrate, polymixin B sulfate, and prednisolone acetate) Otic Suspension in dogs for... Cosmetic Act (21 U.S.C. 360b(c)(2)(F)(ii)), this approval qualifies for 3 years of marketing exclusivity...

  4. Autoradiographic investigations on the prednisolone-induced atrophy and on interdependent reactions in different lymphatic tissues of rabbit

    International Nuclear Information System (INIS)

    Steigueber, F.

    1980-01-01

    Under the application of 3 H-thymidine the method of organ extirpation (thymectomy and appendectomy) was combined with the cell labeling technique. By autoradiographic evaluation of histologic specimens the content of labelled lymphocytes in the examined tissues was determined. Thymus, appendix, subcutaneous lymphatic nodes and spleen were examined. In the thymus the application of prednisolone induced organ atrophy. Appendectomy leads in the thymic marrow to an increase of the mitotic activity. In the appendix the application of prednisolone causes the emptying of basal lymphatic follicles. Thymectomy induces a large increase of the mitotic activity of the lymphatic tissue. Not all lymphatic nodes show identical changes after organ extirpation and after prednisolone application, but considerable differences. Only a decreased proliferation of labled lymphocytes, occuring under prednisolone application, can be detected in the marrow of the mesenteric lymphatic nodes and of the red splenic pulp in the animal with thymectomy. This result is also valid for the marrow of the remaining deep lymphatic nodes, after thymectomy and appendectomy. The lymphocyte counting in the peripheral blood done during prednisolone treatment, does not indicate that the lymphocyte values depend to a notable extent on the previous surgical treatment of the animals. (orig./MG) [de

  5. Comparison of the therapeutic effects of prednisolone and nonsteroidal anti-inflammatory drugs in patients with subacute thyroiditis.

    Science.gov (United States)

    Sato, Junko; Uchida, Toyoyoshi; Komiya, Koji; Goto, Hiromasa; Takeno, Kageumi; Suzuki, Ruriko; Honda, Akira; Himuro, Miwa; Watada, Hirotaka

    2017-01-01

    Subacute thyroiditis is a transient inflammatory thyroid disease of unknown etiology. The primary goal for treatment is to mitigate inflammation. The aim of this retrospective study was to compare the therapeutic effects of prednisolone and nonsteroidal anti-inflammation drugs in patients with subacute thyroiditis. In this study, 53 consecutive Japanese patients who had been diagnosed with were referred to our hospital for further management. After excluding 11 patients (9 did not need treatment, 2 did not meet the criteria for diagnosis of subacute thyroiditis), the remaining 42 patients were treated either with prednisolone (n = 25) or loxoprofen (n = 17). We compared the time periods required for resolution of clinical symptoms and signs and normalization of thyroid function between the two groups. The mean dose of prednisolone was 15.0 (range, 14-16) mg/day and that of loxoprofen was 180 mg/day. The time period to normalization of thyroid function was comparable between the prednisolone and loxoprofen groups (25, 18-36, vs 32, 21-39 days, p = 0.388). However, the time period for resolution of symptoms was shorter under prednisolone than loxoprofen (7, 7-12 days, vs 21, 14-32 days, p thyroiditis was superior to nonsteroidal anti-inflammation drugs with regard to resolution of symptoms.

  6. OPEC chemotherapy (vincristine, prednisolone, etoposide and chlorambucil) for refractory and recurrent Hodgkin's disease.

    Science.gov (United States)

    Barnett, M J; Man, A M; Richards, M A; Waxman, J H; Wrigley, P F; Lister, T A

    1987-01-01

    Fifteen adults with refractory or recurrent Hodgkin's disease were treated with a combination of: vincristine, prednisolone, etoposide and chlorambucil (OPEC). All had previously received mustine, vinblastine, procarbazine and prednisolone (MVPP) and seven had subsequently been treated with alternative regimens. Responses were achieved in four, but complete remission in only one. Toxicity was considerable and five died of treatment related complications. Only two are alive (one in complete remission) more than three years after therapy. The toxicity of the OPEC regimen outweighed its benefit in this group of poor prognosis patients.

  7. Effect of prednisolone on inflammatory markers in pericardial tuberculosis: A pilot study

    Directory of Open Access Journals (Sweden)

    Justin Shenje

    2018-03-01

    Full Text Available Background: Pericardial disorders are a common cause of heart disease, and the most common cause of pericarditis in developing countries is tuberculous (TB pericarditis. It has been shown that prednisolone added to standard anti-TB therapy leads to a lower rate of constrictive pericarditis. We conducted a pilot study to evaluate the effect of adjunctive prednisolone treatment on the concentration of inflammatory markers in pericardial tuberculosis, in order to inform immunological mechanisms at the disease site. Methods: Pericardial fluid, plasma and saliva samples were collected from fourteen patients with pericardial tuberculosis, at multiple time points. Inflammatory markers were measured using multiplex luminex analysis and ELISA. Results: In samples from 14 patients we confirmed a strongly compartmentalized immune response at the disease site and found that prednisolone significantly reduced IL-6 concentrations in plasma by 8 hours of treatment, IL-1beta concentrations in saliva, as well as IL-8 concentrations in both pericardial fluid and saliva by 24 hours. Conclusion: Monitoring the early effect of adjunctive immunotherapy in plasma or saliva is a possibility in pericarditis. Keywords: Tuberculosis, HIV, Pericarditis, Steroids, Treatment monitoring

  8. Topical flurbiprofen or prednisolone. Effect on corneal wound healing in rabbits.

    Science.gov (United States)

    Miller, D; Gruenberg, P; Miller, R; Bergamini, M V

    1981-04-01

    Flurbiprofen is a nonsteroidal anti-inflammatory (NSAI) agent currently undergoing clinical investigation. Anti-inflammatory steroids have long been known to delay the healing of corneal stromal wounds. This was designed to compare the effects of equipotent anti-inflammatory doses of flurbiprofen and of prednisolone acetate on the inflammation and the healing (as measured by the wound bursting pressure) or 4-mm through-and-through incisions treated four times a day for ten postoperative days. The results suggest that flurbiprofen and prednisolone are not different in their effect on both postoperative inflammation and postoperative wound healing. Since NSAI agents and steroids inhibit prostaglandin formation at different enzymatic steps, it is possible that prostaglandins not only are responsible for postoperative inflammation but also are required for postoperative wound healing.

  9. Radioimmunological determination of plasma cortisol following application of a stomatic paste containing prednisolone (DontisolonR)

    International Nuclear Information System (INIS)

    Stehn, H.

    1985-01-01

    A radioimmunological method was used to determine the cortisol plasma levels of 69 patients, treated with a stomatic paste containing prednisolone. Significant changes in plasma cortisol were only established in connection with a dose regimen of 3 times 1.25 mg daily. In isolated cases, however, there were major decreases in response to exposure to prednisolone. Therefore, the anamnestic data of any one patient being prescribed corticoids must be examined with care. (TRV) [de

  10. Mucosal healing with thalidomide in refractory Crohn's disease patients intolerant of anti-TNF-α drugs: report of 3 cases and literature review.

    Science.gov (United States)

    Scribano, Maria Lia; Cantoro, Laura; Marrollo, Marzia; Cosintino, Rocco; Kohn, Anna

    2014-07-01

    Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor necrosis factor-α (TNF-α) activity. Several case reports and some clinical trials have demonstrated its efficacy in the treatment of refractory Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3 patients with moderate-to-severe CD who were not responsive to anti-TNF-α therapies, and review the relevant literature. The first case is of a 28-year-old female affected by Crohn's colitis complicated by a severe fistulizing perianal disease; she was treated with infliximab, adalimumab, and certolizumab pegol, which were stopped because of intolerance. The second case is of a 39-year-old female with fistulizing ileocolitis complicated by severe arthralgias and perianal disease with loss of response to infliximab and intolerance of certolizumab pegol. The third case is of a 39-year-old male with gastric and ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All the 3 cases achieved complete clinical remission and endoscopic healing of mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients who experienced loss of response or were unable to tolerate anti-TNF-α drugs, thalidomide was an effective and well-tolerated therapy for inducing and maintaining long-term remission.

  11. Post-induction residual leukemia in childhood acute lymphoblastic leukemia quantified by PCR correlates with in vitro prednisolone resistance

    DEFF Research Database (Denmark)

    Schmiegelow, K; Nyvold, C; Seyfarth, J

    2001-01-01

    Most prognostic factors in childhood acute lymphoblastic leukemia (ALL) are informative for groups of patients, whereas new approaches are needed to predict the efficacy of chemotherapy for the individual patient. The residual leukemia following 4 weeks of induction therapy with prednisolone......, vincristine, doxorubicin and i.t. methotrexate and the in vitro resistance to prednisolone, vincristine, and doxorubicin were measured in 30 boys and 12 girls with B (n = 34) or T lineage (n = 8) ALL. The residual leukemia was quantified after 2 (MRD-D15, n = 29) and 4 weeks (MRD-PI, n = 42) of induction...... pronounced when B cell precursor and T cell leukemia were analyzed separately (B cell precursor ALL: MRD-PI vs prednisolone LC50: n = 33, rs = 0.47, P = 0.006; T cell ALL: MRD-PI vs prednisolone resistance: n = 8, rs = 0.84, P = 0.009). After a median follow-up of 5.0 years (75% range 3.2-6.9) eight patients...

  12. Testicular lymphocytic vasculitis treated with prednisolone and azathioprine.

    Science.gov (United States)

    Kanzawa, Yohei; Imai, Yukihiro; Mizuno, Yasushi; Nishioka, Hiroaki

    2017-07-01

    Testicular vasculitis is a rare condition and little is known about its morphological features. Herein, we report a case of testicular lymphocytic vasculitis, which is rarely documented, in an elderly man. He presented with left testicular swelling and fever, but without any signs of other organ involvement. He was effectively treated with prednisolone and azathioprine. This case report offers information related to the disease course and the importance of biopsy.

  13. COPD exacerbations in general practice: variability in oral prednisolone courses

    Directory of Open Access Journals (Sweden)

    de Vries Marianne

    2012-01-01

    Full Text Available Abstract Background The use of oral corticosteroids as treatment of COPD exacerbations in primary care is well established and evidence-based. However, the most appropriate dosage regimen has not been determined and remains controversial. Corticosteroid therapy is associated with a number of undesirable side effects, including hyperglycaemias, so differences in prescribing might be relevant. This study examines the differences between GPs in dosage and duration of prednisolone treatment in patients with a COPD exacerbation. It also investigates the number of general practitioners (GPs who adjust their treatment according to the presence of diabetic co-morbidity. Methods Cross-sectional study among 219 GPs and 25 GPs in training, located in the Northern part of the Netherlands. Results The response rate was 69%. Nearly every GP prescribed a continuous dose of prednisolone 30 mg per day. Among GPs there were substantial differences in treatment duration. GPs prescribed courses of five, seven, ten, or fourteen days. A course of seven days was most common. The duration of treatment depended on exacerbation and disease severity. A course of five days was especially prescribed in case of a less severe exacerbation. In a more severe exacerbation duration of seven to fourteen days was more common. Hardly any GP adjusted treatment to the presence of diabetic co-morbidity. Conclusion Under normal conditions GPs prescribe prednisolone quite uniformly, within the range of the current Dutch guidelines. There is insufficient guidance regarding how to adjust corticosteroid treatment to exacerbation severity, disease severity and the presence of diabetic co-morbidity. Under these circumstances, there is a substantial variation in treatment duration.

  14. Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Tânia R.C. Vergara

    2017-09-01

    Conclusions: Short-term use of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4+ cell count without changes to the CD8+ cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication.

  15. Exploratory Study of Total and Free Prednisolone Plasma Exposure and Cushingoid Appearance, Quality of Life and Biochemical Toxicity in Adult Male Kidney Transplant Recipients

    DEFF Research Database (Denmark)

    Bergmann, Troels K; Isbel, Nicole M; Ostini, Remo

    2015-01-01

    relationships between prednisolone exposure and adverse effects. METHODS: Male kidney transplant recipients were recruited for serial blood sampling and assessment of glucocorticoid-related adverse effects including dyslipidaemia, abnormal body fat distribution, Cushingoid appearance and impaired quality...... of life. Total and free prednisolone plasma concentrations were determined using ultra-high-performance liquid chromatography with tandem mass spectrometric detection. Prednisolone exposure was estimated using a limited sampling strategy. RESULTS: Fifty-six patients were recruited. Patients had a mean age...... of 54 years and median time post-transplantation of 75 months. Median prednisolone dose was 5 mg. Mean area under the plasma concentration-time curve was 2390 nmol h/L (±580) (SD) and 175 nmol h/L (±78) for total and free prednisolone, respectively. Waist to upper arm circumference ratio was positively...

  16. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    DEFF Research Database (Denmark)

    Vangsted, A. J.; Soeby, K.; Klausen, T.W.

    2010-01-01

    . We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion...

  17. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome

    NARCIS (Netherlands)

    Teeninga, N.; Kist-van Holthe, J.E.; Rijswijk, N. van; Mos, N.I. de; Hop, W.C.J.; Wetzels, J.F.M.; Heijden, A.J. van der; Nauta, J.

    2013-01-01

    Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69

  18. Intestinal Anisakiasis Treated Successfully with Prednisolone and Olopatadine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Hideki Toyoda

    2016-02-01

    Full Text Available The clinical characteristic of gastrointestinal anisakiasis is severe abdominal pain after eating raw fish. Intestinal anisakiasis is more uncommon than gastric anisakiasis. Most patients with intestinal anisakiasis need hospitalization because anisakiasis can cause intestinal obstruction, ileus, peritonitis or intestinal perforation. We report a case of intestinal anisakiasis. A 43-year-old woman presented with symptoms of intermittent abdominal pain 2 days after eating raw fish. Her brother had eaten the same food and had been suffering from gastric anisakiasis. Abdominal ultrasonography in this patient showed localized jejunal wall thickening with dilated lumen of proximal jejunum and ascites. According to the clinical course and examinations, she was diagnosed with intestinal anisakiasis. Administration of prednisolone 5 mg/day and olopatadine hydrochloride 10 mg/day improved her symptoms quickly without hospitalization. Prednisolone was administered for 10 days, and olopatadine hydrochloride was administered for a total of 6 weeks according to ultrasonographic findings. Six months after the treatment, the abdominal ultrasonography demonstrated normal findings. This case demonstrates that ultrasonography was quite useful for the diagnosis and surveillance of intestinal anisakiasis. Furthermore, treatment with corticosteroid and an antiallergic agent could be an option for patients with intestinal anisakiasis.

  19. Suppression of Immunogenesis When Using Gangleron and Prednisolone

    Energy Technology Data Exchange (ETDEWEB)

    Antonyan, K. A. [Armenian Institute of Haematology and Blood Transfusion, Yerevan, USSR (Armenia)

    1969-07-15

    The paper summarizes the results of research into the effect on haemopoiesis of transplantation of allogenic bone marrow into dogs suffering from depressed haemopoiesis caused by ionizing radiation and a chemical agent (myelosan). Myelotherapy was carried out with the ganglion-blocking agent gangleron (synthesized by the Fine Organic Chemistry Institute of the Armenian Academy of Sciences) and prednisolone. This method of therapy has prevented the development of secondary disease and contributed to a high survival rate. (author)

  20. Optimization of photo-Fenton process for the treatment of prednisolone.

    Science.gov (United States)

    Díez, Aida María; Ribeiro, Ana Sofia; Sanromán, Maria Angeles; Pazos, Marta

    2018-03-29

    Prednisolone is a widely prescribed synthetic glucocorticoid and stated to be toxic to a number of non-target aquatic organisms. Its extensive consumption generates environmental concern due to its detection in wastewater samples at concentrations ranged from ng/L to μg/L that requests the application of suitable degradation processes. Regarding the actual treatment options, advanced oxidation processes (AOPs) are presented as a viable alternative. In this work, the comparison in terms of pollutant removal and energetic efficiencies, between different AOPs such as Fenton (F), photo-Fenton (UV/F), photolysis (UV), and hydrogen peroxide/photolysis (UV/H 2 O 2 ), was carried out. Light diode emission (LED) was the selected source to provide the UV radiation. The UV/F process revealed the best performance, reaching high levels of both degradation and mineralization with low energy consumption. Its optimization was conducted and the operational parameters were iron and H 2 O 2 concentrations and the working volume. Using the response surface methodology with the Box-Behnken design, the effect of independent variables and their interactions on the process response were effectively evaluated. Different responses were analyzed taking into account the prednisolone removal (TOC and drug abatements) and the energy consumptions associated. The obtained model showed an improvement of the UV/F process when treating smaller volumes and when adding high concentrations of H 2 O 2 and Fe 2+ . The validation of this model was successfully carried out, having only 5% of discrepancy between the model and the experimental results. Finally, the performance of the process when having a real wastewater matrix was also tested, achieving complete mineralization and detoxification after 8 h. In addition, prednisolone degradation products were identified. Finally, the obtained low energy permitted to confirm the viability of the process.

  1. Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor

    Directory of Open Access Journals (Sweden)

    Dokter Wim

    2010-06-01

    Full Text Available Abstract Background Glucocorticoids (GCs control expression of a large number of genes via binding to the GC receptor (GR. Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT and mice that have lost the ability to form GR dimers (GRdim. Results The GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GRdim mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GRdim mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GRdim mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization. Conclusions This study on prednisolone-induced effects in livers of WT and GRdim mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs.

  2. Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

    2014-01-01

    Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six e...

  3. Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Decourt, Boris; Drumm-Gurnee, Denise; Wilson, Jeffrey; Jacobson, Sandra; Belden, Christine; Sirrel, Sherye; Ahmadi, Michael; Shill, Holly; Powell, Jessica; Walker, Aaron; Gonzales, Amanda; Macias, Mimi; Sabbagh, Marwan N

    2017-01-01

    To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. O renascimento de um fármaco: talidomida The rebirth of a drug: thalidomide

    Directory of Open Access Journals (Sweden)

    Lídia Moreira Lima

    2001-10-01

    Full Text Available Thalidomide, first synthesized in 1953, was widely prescribed for morning sickness of pregnant women from 1957 to 1961, when it was found to be seriously teratogenic, having caused serious birth defect. Nowadays, a quarter of a century later, it appears that it may be a miracle drug for such diseases as leprosy, AIDS, cancer and tuberculosis.

  5. Talidomida, contextos históricos y éticos Thalidomide, historical and ethical contexts

    Directory of Open Access Journals (Sweden)

    José Ángel Chávez Viamontes

    2009-12-01

    Full Text Available A finales de la década del 50, en Europa, Australia, Japón y varios países africanos, la talidomida provocó más de 10 000 casos de defectos congénitos en hijos de madres que la consumieron durante el embarazo. En 1962, es retirada del mercado. Tres décadas después, se reivindica su prescripción en el manejo de enfermedades de pronóstico desfavorable. Sus propiedades antiangiogénicas e inmunorreguladoras la hacen diferente al fármaco de los años 50 en gran medida. A pesar de poseer las mismas propiedades farmacológicas y riesgos teratogénicos, la molécula talidomida tiene otras las indicaciones, dosis, campos de aplicación y condiciones legales de uso. Esta revisión tiene como objetivo reseñar los contextos históricos y éticos que condicionaron la proscripción de la talidomida a principios de los años 60, así como las actuales condiciones clínicas en que se usan o ensayan actualmente sus efectos terapéuticos.In Europe, Australia, Japan, and some African countries in the late 50's, Thalidomide caused more than 10 000 cases of congenital defects in children whose mothers consumed it during pregnancy. In 1962, it was withdrawn from market. Thirty years later, it is used for the management diseases with unfavorable prognosis. Its antiangiogenic and immunoregulatory characteristics distinguish it from the drug of 1950. Although containing the same pharmacological features and teratogenic risks, the molecule thalidomide does have other prescriptions, doses, application fields, and lawful conditions of use. This revision points out both the historical and ethical contexts, which conditioned the banning of Thalidomide in the early 60's, and the clinical conditions in which its therapeutic effects are used and studied today.

  6. Measurements of the phase behavior of ternary systems of interest to the gas process: II : the system CO2 + methanol + prednisolone

    NARCIS (Netherlands)

    Shariati - Sarabi, A.; Tesauro, C.; Reverchon, E.; Peters, C.J.

    2012-01-01

    In this work, the phase behavior of the ternary system carbon dioxide + methanol + prednisolone has been studied experimentally. For this purpose, carbon dioxide has been chosen as the anti-solvent gas, methanol as the organic solvent, and prednisolone as the model drug that should be micronized

  7. 21 CFR 520.2345h - Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline hydrochloride, sodium novobiocin, and... ANIMAL DRUGS § 520.2345h Tetracycline hydrochloride, sodium novobiocin, and prednisolone tablets. (a... the first stage of parturition when administered during the last trimester of pregnancy and may...

  8. Thalidomide inhibits UVB-induced mouse keratinocyte apoptosis by both TNF-α-dependent and TNF-α-independent pathways

    NARCIS (Netherlands)

    Lu, K.Q.; Brenneman, S.; Burns Jr., R.; Vink, A.; Gaines, E.; Haake, A.; Gaspari, A.

    2003-01-01

    Background: Thalidomide is an anti-inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti-inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor-alfa (TNF-α) production by monocytes. However, its

  9. Effects of Consolidation Stress State on Normally Consolidated Clay

    DEFF Research Database (Denmark)

    Lade, Poul V.

    2000-01-01

    The effect of consolidation stress state on the stress-strain and strength characteristics has been studied from experiments on undisturbed block samples of a natural, normally consolidated clay known as San Francisco Bay Mud. The results of experiments on K0-consolidated, hollow cylinder specimens...... and on isotropically consolidated, cubical specimens, both tested in triaxial compression and extension, clearly showed the influence of the undisturbed fabric as well as the effect of the initial consolidation stress states. While the K0-consolidated specimens appeared to retain their original fabric and exhibit...

  10. The efficacy of cyclosporine A in cats with presumed atopic dermatitis: a double blind, randomised prednisolone-controlled study.

    Science.gov (United States)

    Wisselink, Marinus A; Willemse, Ton

    2009-04-01

    The objective of this study was to compare the efficacy of cyclosporine A (CsA) and prednisolone in feline atopic dermatitis (AD) in a randomised, controlled double blind study. Twenty-nine cats with feline AD were randomly allocated to two groups. Eleven cats were treated orally with prednisolone (1mg/kg SID) and 18 were treated with CsA (5mg/kg/day) for 4 weeks. At day 0 (D0) and D28, skin lesions were graded by means of the canine atopic dermatitis extent and severity index (CADESI). Skin biopsies and intradermal allergy tests were performed at D0 and blood samples for haematology and serum biochemistry were collected at D0 and D28. During the trial the cat owners were asked to evaluate the intensity of the pruritus once weekly on a linear analog scale and to record side effects. Based on the CADESI there was no significant difference between the two groups in the amount of remission (P=0.0562) or in the number of cats that improved by >25% (P=0.0571). The effect of CsA and prednisolone on pruritus as evaluated by the owners was not significantly different (P=0.41) between the two groups. No serious side effects were observed. The conclusion was that CsA is an effective alternative to prednisolone therapy in cats with presumed atopic dermatitis.

  11. Prednisolone Trial: Study protocol for a randomised controlled trial of prednisolone for women with idiopathic recurrent miscarriage and raised levels of uterine natural killer (uNK cells in the endometrium

    Directory of Open Access Journals (Sweden)

    Drury Jo

    2009-11-01

    Full Text Available Abstract Background Idiopathic recurrent miscarriage is defined as 3 consecutive pregnancy losses with no contributing features found on investigations. At present there are no treatments of proven efficacy for idiopathic recurrent miscarriage. Uterine natural killer (uNK cells, the most predominant leucocyte in the endometrium are adjacent to foetal trophoblast cells and thought to be involved in implantation. The exact mechanisms of how uNK cells affect implantation are not clear but are probably through the regulation of angiogenesis. Multiple studies have shown an association between high density of uterine natural killer cells and recurrent miscarriage. We have shown that prednisolone reduces the number of uNK cells in the endometrium. The question remains as to whether reducing the number of uNK cells improves pregnancy outcome. Methods We propose a randomised, double-blind, placebo controlled trial of prednisolone with a pilot phase to assess feasibility of recruitment, integrity of trial procedures, and to generate data to base future power calculations. The primary aim is to investigate whether prednisolone therapy during the first trimester of pregnancy is able to improve live birth rates in patients with idiopathic recurrent miscarriage and raised uNK cells in the endometrium. Secondary outcomes include conception rate, karyotype of miscarriage, miscarriages (first and second trimester, stillbirths, pregnancy complications, gestational age at delivery, congenital abnormality and side effects of steroids. The trial has 2 stages: i screening of non-pregnant women and ii randomisation of the pregnant cohort. All patients who fit the inclusion criteria ( Trial Registration Current Controlled Trials ISRCTN28090716

  12. Prednisolone Delivery Platforms: Capsules and Beads Combination for a Right Timing Therapy.

    Directory of Open Access Journals (Sweden)

    Andrea Cerciello

    Full Text Available In this work, a platform of alginate beads loaded with Prednisolone in hypromellose/gellan gum capsules (F6/Cps able to delay steroidal anti-inflammatory drug (SAID release as needed for chronotherapy of rheumatoid arthritis is proposed. Rheumatoid arthritis, showing a worsening in symptoms in the morning upon waking, is a pathology that can benefit from chronotherapy. With the aim to maximize prednisolone therapeutic action allowing the right timing of glucocorticoid therapy, different engineered microparticles (gel-beads were manufactured using prilling (laminar jet break-up as micro-encapsulation technique and Zn-alginate as gastroresistant carrier. Starting from various feed solutions and process parameters, the effect of the variables on particles size, morphology, solid state properties and drug release was studied. The optimization of operative and prilling/ionotropic gelation variables led to microspheres with almost spherical shape and a narrow dimensional range. The feed solution with the highest alginate (2.5% w/v amount and drug/polymer ratio (1:5 w/w gave rise to the highest encapsulation efficiency (78.5% as in F6 formulation. As to drug release, F6 exhibited an interesting dissolution profile, releasing about 24% of the drug in simulated gastric fluid followed by a more sustained profile in simulated intestinal fluid. #F6, acting as a gastro-resistant and delayed release formulation, was selected for in vivo studies on male Wistar rats by means of a carrageenan-induced oedema model. Finally, this efficacious formulation was used as core material for the development of a final dosage form: F6/Cps allowed to significantly reduce prednisolone release in simulated gastric fluid (12.6% and delayed drug release up to about 390 minutes.

  13. Effects of iloprost on bleomycin-induced pulmonary fibrosis in rats compared with methyl-prednisolone

    Directory of Open Access Journals (Sweden)

    Z.A. Aytemur

    2012-11-01

    Full Text Available Objective: Prostacyclin (PGI2 has been shown to inhibit the expression of pro-inflammatory and pro-fibrotic mediators in pulmonary fibrosis. In this study, we aimed to test the preventive effects of intraperitoneally administered iloprost, a stable PGI2 analog, on bleomycin-induced pulmonary fibrosis in rats and to compare the effects of iloprost with the effects of methyl-prednisolone, a traditional therapy. Methods: Rats were randomly allocated into four groups: 1. Saline alone (n = 6; 2. Bleomycin + placebo (n = 7; 3. Bleomycin + methyl-prednisolone (n = 7; 4. Bleomycin + iloprost (n = 7. Fibrotic changes in the lungs were demonstrated by analyzing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content. Results: Fibrosis was made in the lungs of rats by bleomycin experimentally. Fibrosis scores in the methyl-prednisolone and the iloprost groups were significantly lower than in the placebo group (p < 0.05. Furthermore, the score of the iloprost group was significantly lower than the score of the methyl-prednisolone group. The hydroxyproline content was significantly less in the methyl-prednisolone and the iloprost groups (p < 0.05. In the placebo group, the neutrophil percentage in bronchoalveolar lavage was significantly higher than in the other groups, whereas the macrophage percentage in placebo group was significantly lower (p < 0.05. Conclusion: Iloprost has protective effect on the pulmonary fibrosis induced by bleomycin and it may be more effective in decreasing fibrotic changes than methyl-prednisolone. Resumo: Objetivo: A prostaciclina (PGI2 é conhecida por inibir a expressão de mediadores pró-inflamatórios e pró-fibróticos na fibrose pulmonar. Neste estudo, procurou-se testar os efeitos preventivos do iloprost administrado por via intraperitoneal, um análogo estável do PGI2, na fibrose

  14. Layer-by-layer assembled magnetic prednisolone microcapsules (MPC) for controlled and targeted drug release at rheumatoid arthritic joints

    Energy Technology Data Exchange (ETDEWEB)

    Prabu, Chakkarapani [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli, Tamil Nadu (India); Latha, Subbiah, E-mail: lathasuba2010@gmail.com [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli, Tamil Nadu (India); Selvamani, Palanisamy [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli, Tamil Nadu (India); Ahrentorp, Fredrik; Johansson, Christer [Acreo Swedish ICT AB, Arvid Hedvalls Backe 4, Göteborg (Sweden); Takeda, Ryoji; Takemura, Yasushi [Electrical & Computer Engineering & Faculty of Engineering Division of Intelligent Systems Engineering, Yokohama National University (Japan); Ota, Satoshi [Department of Electrical and Electronic Engineering, Shizuoka University (Japan)

    2017-04-01

    We report here in about the formulation and evaluation of Magnetic Prednisolone Microcapsules (MPC) developed in order to improve the therapeutic efficacy relatively at a low dose than the conventional dosage formulations by means of magnetic drug targeting and thus enhancing bioavailability at the arthritic joints. Prednisolone was loaded to poly (sodium 4-styrenesulfonate) (PSS) doped calcium carbonate microspheres confirmed by the decrease in surface area from 97.48 m{sup 2}/g to 12.05 of m{sup 2}/g by BET analysis. Adsorption with oppositely charged polyelectrolytes incorporated with iron oxide nanoparticles was confirmed through zeta analysis. Removal of calcium carbonate core yielded MPC with particle size of ~3.48 µm, zeta potential of +29.7 mV was evaluated for its magnetic properties. Functional integrity of MPC was confirmed through FT-IR spectrum. Stability studies were performed at 25 °C±65% relative humidity for 60 days showed no considerable changes. Further the encapsulation efficiency of 63%, loading capacity of 18.2% and drug release of 88.3% for 36 h and its kinetics were also reported. The observed results justify the suitability of MPC for possible applications in the magnetic drug targeting for efficient therapy of rheumatoid arthritis. - Highlights: • Development of magnetic prednisolone microcapsules (MPC). • Physicochemical, pharmaceutical and magnetic properties of MPC were characterized. • Multiple layers of alternative polyelectrolytes prolonged prednisolone release time. • MPC is capable for targeted and sustained release rheumatoid arthritis therapy.

  15. Nonlinear Finite Strain Consolidation Analysis with Secondary Consolidation Behavior

    Directory of Open Access Journals (Sweden)

    Jieqing Huang

    2014-01-01

    Full Text Available This paper aims to analyze nonlinear finite strain consolidation with secondary consolidation behavior. On the basis of some assumptions about the secondary consolidation behavior, the continuity equation of pore water in Gibson’s consolidation theory is modified. Taking the nonlinear compressibility and nonlinear permeability of soils into consideration, the governing equation for finite strain consolidation analysis is derived. Based on the experimental data of Hangzhou soft clay samples, the new governing equation is solved with the finite element method. Afterwards, the calculation results of this new method and other two methods are compared. It can be found that Gibson’s method may underestimate the excess pore water pressure during primary consolidation. The new method which takes the secondary consolidation behavior, the nonlinear compressibility, and nonlinear permeability of soils into consideration can precisely estimate the settlement rate and the final settlement of Hangzhou soft clay sample.

  16. Oral prednisolone for 4 days does not increase exercise tolerance in men with COPD

    DEFF Research Database (Denmark)

    Karlsson, S L; Backer, V; Godtfredsen, Nina Skavlan

    2018-01-01

    One of the primary objectives in management of chronic obstructive pulmonary disease (COPD) is preventing decrease in lung function and reducing the annual number of acute exacerbations of COPD (AECOPD). An oral course of systemic corticosteroids is a commonly used treatment in AECOPD. We...... hypothesize that this treatment also increases exercise performance and decreases muscle fatigue. In a randomized double-blinded, parallel, placebo-controlled trial, we investigated 14 men (8 on prednisolone 37.5 mg vs. 6 on placebo) with severe and very severe COPD. For 5 consecutive days, the patients...... out after 40 minutes of cycling at 40% of maximal effort. No differences between groups were found for TTE, lung function or maximal inspiratory or expiratory pressure, however, patients on prednisolone showed significant increased MVC: median 5.15 [3.35; 9.15] against placebo: -2 [-5.57; 3.95] ( p...

  17. Consolidated financial statements

    OpenAIRE

    Blaha, Miroslav

    2010-01-01

    This work provides basic information about consolidation and consolidated financial statements. In the beginning there are definisions of the members of the group under discussion and their relationship. Hereafter concepts of consolidation, accounting methods and methods of consolidation are discussed. It also compares approach of different accounting systems to consolidation.

  18. Living with thalidomide: health status and quality of life at 40 years.

    Science.gov (United States)

    Bent, N; Tennant, A; Neumann, V; Chamberlain, M A

    2007-06-01

    Thalidomide was first synthesized in 1953 and was subsequently marketed as a mild hypnotic and sedative in more than 20 countries. By 2001 it was estimated that there were 5,000 survivors from the 10,000 - 12,000 babies who were, as a result, born with severe abnormalities. For these survivors, recent concerns have emerged about their physical state, in particular their levels of pain and their ability to maintain independence. It was therefore wished to ascertain health status and current concerns amongst a sample of survivors living in the UK. A combination of qualitative and quantitative methodologies was employed. Qualitative interviews were undertaken with a sample drawn from the population affected by thalidomide known to the Thalidomide Trust. Selection of participants was based upon a theoretical sample frame. Postal questionnaires to examine health status and various psychosocial aspects concerned with living with the consequences of thalidomide were sent subsequently to these same participants and to a random sample of those not originally drawn for the qualitative interviews. For the qualitative interviews, 28 agreed to take part; two refused and the remainder did not respond. Those agreeing to interview were representative of the original compensation bands (Chi-Square = 3.929; p = 0.416). Several themes emerged from these interviews, including the effects on work and career; coping in terms of attitude to life, self-image, confidence, self-esteem, stress and emotion; relationships, independent living issues and emergent problems such as pain, quality of life, and anxiety about the future. A postal questionnaire was then sent to those who had agreed to interview (28), plus a random sample of the remaining group who were not initially chosen for the qualitative interviews. In total 82 people were sent the questionnaire, of whom 41 (50%) responded. Two-thirds of responders were female. Seven out of ten lived with a partner, and over half (56%) had

  19. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary hemorrhagic telangiectasia: results of a prospective phase II clinical trial

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Caherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2016-01-01

    Summary Background Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anemia. Multiple therapeutic approaches have been tried, but they are largely palliative with variable results.We aimed to assess the efficacy of thalidomide in reducing epistaxis in patients with HHT refractory to standard therapy. Methods HHT patients with severe recurrent epistaxis refractory to mini-invasive surgical procedures were included in an open label, phase II, prospective, non-randomized, single-centre study. Thalidomide was administered at a starting dose of 50 mg/day orally. In the event of no response, thalidomide dosage was increased by 50 mg/day every four weeks until response to a maximum dose of 200 mg/day. After response achievement, patients were treated for eight to16 additional weeks. Monthly follow-up was based on the epistaxis severity score and transfusion need, with adverse events being reported (ClinicalTrials.gov Identifier: NCT01485224). Findings Thirty-one patients, mean age 62∙6 (SD 11∙1) years, were enrolled (median follow-up 15∙9 months, 25th-75th 10∙1-22∙3). Treatment induced cessation of bleeding in three cases (9∙7%) and a significant decrease in all epistaxis parameters in 28 cases (90∙3%). Twenty-five patients (80∙7%) obtained remission with 50 mg/day of thalidomide, five (16∙1%) with 100 mg/day and one (3∙2%) with 150 mg/day. Treatment significantly increased hemoglobin levels (pepistaxis in HHT patients, allowing for a rapid, often durable clinical improvement. Funding Telethon Foundation PMID:26686256

  20. Dose uniformity of loteprednol etabonate ophthalmic gel (0.5%) compared with branded and generic prednisolone acetate ophthalmic suspension (1%).

    Science.gov (United States)

    Marlowe, Zora T; Davio, Stephen R

    2014-01-01

    Loteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax®) is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel at rest and a shear thinning fluid when expressed through a dropper tip. The present study was undertaken to determine how the nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone acetate ophthalmic suspension 1% (Pred Forte®) and a generic prednisolone acetate suspension 1% were used as comparators. Drug concentrations of LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were determined following simulated dosing - consisting of 2 drops, expressed four times daily for 2 weeks, with bottles that were shaken or not shaken immediately prior to expressing the drops. Drug concentrations were determined using a reverse-phase high-performance liquid chromatography (HPLC) method and reported as a percentage of the declared (labeled) concentration. Comparative kinetics of drug particle sedimentation were also determined for each formulation, using dispersion analysis under gravity. Mean drug concentrations in drops of all three formulations were within a few percentage points of the declared concentration when the bottles were shaken for 5 seconds prior to dispensing. Only LE ophthalmic gel showed consistent and on-target concentrations when the bottles were unshaken prior to dispensing, with a mean (standard deviation [SD]) percent declared concentration of 102% (1.92%) over the 2-week dosing regimen. Drug concentrations for the branded and generic prednisolone acetate suspensions following expression from unshaken bottles were highly variable (overall relative SDs of 16.8% and 20.3%, respectively), with mean concentrations for both falling significantly below the declared concentration for drops expressed at the beginning of the 2-week dosing regimen and significantly above the declared concentration for drops expressed near the end of the dosing

  1. Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

    Science.gov (United States)

    García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

    2017-12-01

    Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Successful Prednisolone Therapy in Elderly Patients with Severe Forms of Henoch–Schönlein Purpura Nephritis

    Directory of Open Access Journals (Sweden)

    Saiko Kato-Okada

    2015-01-01

    Full Text Available Introduction Recently, Henoch–Schönlein purpura (HSP has been observed in elderly people, although it was believed to be uncommon in these subjects. The increased risks of developing end-stage renal disease (ESRD in adults in comparison with children were highlighted by different studies; however, limited data are available on the treatment of HSP nephritis in adults. Methods Between 2002 and 2008, five elderly Japanese patients (>65 years old (mean age, 68 years, ranging from 65 to 72 with severe forms of HSP nephritis were entered into a prospective study to evaluate prednisolone therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and crescentic glomeruli. Results At the last follow-up, 4–10 years after initiation of the therapy, four patients had clinically recovered and one died of lung cancer. No patients developed ESRD. The clinical outcome seemed to be correlated with glomerular activity (massive proteinuria and crescent formation. In spite of a relatively large dose of prednisolone, a few adverse effects, such as insomnia and skin lesions, were observed. Discussion Our preliminary small study suggests that renal outcome as well as survival of elderly patients with severe forms of HSP might be altered by aggressive prednisolone therapy.

  3. Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.

    Directory of Open Access Journals (Sweden)

    Alessia Nicotra

    Full Text Available Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females and 17 controls (37.9±9.0 years; 8 females demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1, L5 radiculopathic sensory impairment (n = 1 and cervical myelopathy (n = 1. In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002 ([95% CI], p-value and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089 in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232 and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169.We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.

  4. 20 CFR 702.345 - Formal hearings; consolidated issues; consolidated cases.

    Science.gov (United States)

    2010-04-01

    ...; consolidated cases. (a) When one or more additional issues are raised by the administrative law judge pursuant... Administrative Law Judge may consolidate such cases for hearing. ...; consolidated cases. 702.345 Section 702.345 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT...

  5. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

    Science.gov (United States)

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-07-01

    Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

  6. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    International Nuclear Information System (INIS)

    Vangsted, Annette J; Rasmussen, Henrik B; Søeby, Karen; Klausen, Tobias W; Abildgaard, Niels; Andersen, Niels F; Gimsing, Peter; Gregersen, Henrik; Vogel, Ulla; Werge, Thomas

    2010-01-01

    The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome

  7. Stress degradation studies and development of stability-indicating TLC-densitometry method for determination of prednisolone acetate and chloramphenicol in their individual and combined pharmaceutical formulations

    Directory of Open Access Journals (Sweden)

    Musharraf Syed

    2012-01-01

    Full Text Available Abstract A rapid and reproducible stability indicating TLC method was developed for the determination of prednisolone acetate and chloramphenicol in presence of their degraded products. Uniform degradation conditions were maintained by refluxing sixteen reaction mixtures for two hours at 80°C using parallel synthesizer including acidic, alkaline and neutral hydrolysis, oxidation and wet heating degradation. Oxidation at room temperature, photochemical and dry heating degradation studies were also carried out. Separation was done on TLC glass plates, pre-coated with silica gel 60F-254 using chloroform: methanol (14:1 v/v. Spots at Rf 0.21 ± 0.02 and Rf 0.41 ± 0.03 were recognized as chloramphenicol and prednisolone acetate, respectively. Quantitative analysis was done through densitometric measurements at multiwavelength (243 nm, λmax of prednisolone acetate and 278 nm, λmax of chloramphenicol, simultaneously. The developed method was optimized and validated as per ICH guidelines. Method was found linear over the concentration range of 200-6000 ng/spot with the correlation coefficient (r2 ± S.D. of 0.9976 ± 3.5 and 0.9920 ± 2.5 for prednisolone acetate and chloramphenicol, respectively. The developed TLC method can be applied for routine analysis of prednisolone acetate and chloramphenicol in presence of their degraded products in their individual and combined pharmaceutical formulations.

  8. Dose uniformity of loteprednol etabonate ophthalmic gel (0.5% compared with branded and generic prednisolone acetate ophthalmic suspension (1%

    Directory of Open Access Journals (Sweden)

    Marlowe ZT

    2013-12-01

    Full Text Available Zora T Marlowe, Stephen R DavioPharmaceutical Product Development, Global Pharmaceutical Research and Development, Bausch and Lomb, Inc, Rochester, NY, USAIntroduction: Loteprednol etabonate (LE ophthalmic gel 0.5% (Lotemax® is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel at rest and a shear thinning fluid when expressed through a dropper tip. The present study was undertaken to determine how the nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone acetate ophthalmic suspension 1% (Pred Forte® and a generic prednisolone acetate suspension 1% were used as comparators.Methods: Drug concentrations of LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were determined following simulated dosing – consisting of 2 drops, expressed four times daily for 2 weeks, with bottles that were shaken or not shaken immediately prior to expressing the drops. Drug concentrations were determined using a reverse-phase high-performance liquid chromatography (HPLC method and reported as a percentage of the declared (labeled concentration. Comparative kinetics of drug particle sedimentation were also determined for each formulation, using dispersion analysis under gravity.Results: Mean drug concentrations in drops of all three formulations were within a few percentage points of the declared concentration when the bottles were shaken for 5 seconds prior to dispensing. Only LE ophthalmic gel showed consistent and on-target concentrations when the bottles were unshaken prior to dispensing, with a mean (standard deviation [SD] percent declared concentration of 102% (1.92% over the 2-week dosing regimen. Drug concentrations for the branded and generic prednisolone acetate suspensions following expression from unshaken bottles were highly variable (overall relative SDs of 16.8% and 20.3%, respectively, with mean concentrations for both falling significantly

  9. Evaluation of Danazol, Cyclosporine, and Prednisolone as Single Agent or in Combination for Paroxysmal Nocturnal Hemoglobinuria

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    Kanjaksha Ghosh

    2013-12-01

    Full Text Available OBJECTIVE: The responses of 32 patients with paroxysmal nocturnal hemoglobinuria (PNH were assessed after the patients were put on various combinations of danazol, prednisolone, and cyclosporine. METHODS: Nineteen males and 13 females aged between 14 and 60 years with confirmed diagnosis of PNH were treated with danazol (4, danazol + cyclosporine (7, cyclosporine (1, and prednisolone + danazol (20. Response to these interventions was assessed regularly. Danazol was added to cyclosporine in patients with aplastic bone marrow after 3 months of cyclocporine use only unless the former therapy was successful. Four patients with aplastic marrow received only danazol because they had renal insufficiency at presentation. Patients were evaluated with regular complete blood count and routine liver and renal function tests. RESULTS: One patient responded to cyclosporine only. Thirteen of 32 patients (40% had complete response, 12/32 patients (37% had partial response leading to freedom from red cell transfusion, and 2/32 (7% had no response. Five patients (16% died due to thrombosis or hemorrhage within 3 months of therapy before their response to therapy could be assessed. The median period of review of the cases was 4 years and 6 months. CONCLUSION: Danazol is a useful addition to PNH therapy both in combination with cyclosporine for hypoplastic PNH and with prednisolone for other forms of PNH, and this therapy could be a good alternative where eculizumab and anti-lymphocyte globulin cannot be used for various reasons.

  10. Complement activation capacity in plasma before and during high-dose prednisolone treatment and tapering in exacerbations of Crohn's disease and ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Baatrup Gunnar

    2005-09-01

    Full Text Available Abstract Background Ulcerative colitis (UC and Crohn's disease (CD are characterized by intestinal inflammation mainly caused by a disturbance in the balance between cytokines and increased complement (C activation. Our aim was to evaluate possible associations between C activation capacity and prednisolone treatment. Methods Plasma from patients with exacerbations of UC (n = 18 or CD (n = 18 were collected before and during high dose prednisolone treatment (1 mg/kg body weight and tapering. Friedman's two way analysis of variance, Mann-Whitney U test and Wilcoxon signed-rank sum test were used Results Before treatment, plasma from CD patients showed significant elevations in all C-mediated analyses compared to the values obtained from 38 healthy controls (p Conclusion Our findings indicate that C activation capacity is up-regulated significantly in plasma from CD patients. The decreases observed after prednisolone treatment reflect a general down-regulation in immune activation.

  11. After thalidomide - do we have the right balance between public health and intellectual property.

    Science.gov (United States)

    Feldschreiber, Peter; Breckenridge, Alasdair

    2015-01-01

    The current European regulatory and consumer protection legal framework is the legacy of Thalidomide. The disaster led to the introduction of systematic biological and clinical data to endorse the safety and efficacy of new medicines. The European Medicines Directive outlined the pre-clinical, clinical data and product information to evaluate an appropriate benefit. Risk profile of new medicines and also allowed innovative companies to extend patent protection and data/marketing exclusivity periods to compensate for the cost for research and development. However in recent years it has become apparent that the costs and time for research and development are becoming increasingly burdensome, particularly for new drugs with recently discovered mechanisms of action for cancers and neurodegenerative disorders. The costs of development and the commercial uncertainty of such products is reducing commercialisation of these medicines. There is now considerable debate in the regulatory community as to how this regulatory burden may be eased by making earlier review of benefit risk and hence earlier access to authorised medicines. The Courts are moving away from the wide definition of medicinal product to a more nuanced view of the biological and clinical therapeutic mechanisms to satisfy the 'functional' limb definition in the Directive. This may be a move away from the rigorous scientific methodology generated after thalidomide. We discuss the ethical and public health implications of this shift in policy and the implications for intellectual property mechanisms currently available to protect the commercial needs of companies.

  12. A multicenter randomized controlled fellow eye trial of pulse-dosed difluprednate 0.05% versus prednisolone acetate 1% in cataract surgery.

    Science.gov (United States)

    Donnenfeld, Eric D; Holland, Edward J; Solomon, Kerry D; Fiore, Jay; Gobbo, Anthony; Prince, Jessica; Sandoval, Helga P; Shull, Emily R; Perry, Henry D

    2011-10-01

    To compare the effects of 2 corticosteroids on corneal thickness and visual acuity after cataract surgery. Multicenter, randomized, contralateral-eye, double-masked trial. Fifty-two patients (104 eyes) underwent bilateral phacoemulsification. The first eye randomly received difluprednate 0.05% or prednisolone acetate 1%; the fellow eye received the alternative. Before surgery, 7 doses were administered over 2 hours; 3 additional doses were given after surgery, before discharge. For the remainder of the day, corticosteroids were administered every 2 hours, then 4 times daily during week 1 and twice daily during week 2. Corneal pachymetry, visual acuity, and corneal edema were evaluated before surgery and at days 1, 15, and 30 after surgery. Endothelial cell counts were evaluated before surgery and at 30 days after surgery. Retinal thickness was evaluated before surgery and at 15 and 30 days after surgery. Corneal thickness at day 1 was 33 μm less in difluprednate-treated eyes (P = .026). More eyes were without corneal edema in the difluprednate group than in the prednisolone group at day 1 (62% vs 38%, respectively; P = .019). Uncorrected and best-corrected visual acuity at day 1 were significantly better with difluprednate than prednisolone by 0.093 logMAR lines (P = .041) and 0.134 logMAR lines (P eyes at day 30 (P eyes (P = .011). In this high-dose pulsed-therapy regimen, difluprednate reduced inflammation more effectively than prednisolone acetate, resulting in more rapid return of vision. Difluprednate was superior at protecting the cornea and reducing macular thickening after cataract surgery. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Effects of timing of prednisolone on the duration of early morning stiffness, pain and disease activity score (das-28) in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Gul, H.; Nasim, A.; Salim, B.

    2017-01-01

    To determine the effects of timing of prednisolone on duration of early morning stiffness, pain score, number of swollen and tender joints, erythrocyte sedimentation rate (ESR) and disease activity score 28 (DAS-28) in joints in patients with rheumatoid arthritis. Study Design: It was quasi experimental study. Place and Duration of Study: This study was conducted in the department of rheumatology Fauji Foundation Hospital Rawalpindi over a period of 3 months, from Dec 2015 to Feb 2016. Material and Methods: Total sample size of 85 was calculated by using non probability consecutive sampling technique. Patients with established rheumatoid arthritis diagnosed on the basis of ACR 1987 criteria were included in the study. All these patients had a disease duration of minimum 6 months and were on disease modifying anti rheumatic drugs and were taking =7.5mg of prednisolone and these patients were treated with the same dose of prednisolone given in morning at 8:00 A.M. for the first 15 days followed by treatment with same single daily dose of prednisolone given at the night 10:00 P.M. for next 15 days. This study compared duration of early morning stiffness, pain scores, number of swollen and tender joints, DAS-28 and ESR on day 15th and day 30th. Results: A total of 85 patients of established rheumatoid arthritis were included in the study. All patients were female with a mean duration of disease of 7.87 +- 6.41 years. The mean age of patients was 49.39 +- 10.24 years. Mean of pain score, duration of morning stiffness, DAS-28, number of tender and swollen joint count, and ESR was decreased in patients who took prednisolone at 10:00 pm and had significant statistical difference (p-value<0.001). Conclusions: Administration of low dose of prednisolone at night has good effects on duration of early morning stiffness, pain scores, number of swollen and tender joints, ESR and DAS-28. (author)

  14. Effectiveness of 32 versus 20 weeks of prednisolone in leprosy patients with recent nerve function impairment: A randomized controlled trial.

    Science.gov (United States)

    Wagenaar, Inge; Post, Erik; Brandsma, Wim; Bowers, Bob; Alam, Khorshed; Shetty, Vanaja; Pai, Vivek; Husain, Sajid; Sigit Prakoeswa, Cita Rosita; Astari, Linda; Hagge, Deanna; Shah, Mahesh; Neupane, Kapil; Tamang, Krishna Bahadur; Nicholls, Peter; Richardus, Jan Hendrik

    2017-10-01

    While prednisolone is commonly used to treat recent nerve function impairment (NFI) in leprosy patients, the optimal treatment duration has not yet been established. In this "Treatment of Early Neuropathy in Leprosy" (TENLEP) trial, we evaluated whether a 32-week prednisolone course is more effective than a 20-week course in restoring and improving nerve function. In this multi-centre, triple-blind, randomized controlled trial, leprosy patients who had recently developed clinical NFI (leprosy patients. Twenty weeks is therefore the preferred initial treatment duration for leprosy neuropathy, after which likely only a minority of patients require further individualized treatment.

  15. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    M. Dolenc-Voljč

    2013-11-01

    Full Text Available Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg.

  16. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Science.gov (United States)

    Dolenc-Voljč, M.; Jurčić, V.; Hočevar, A.; Tomšič, M.

    2013-01-01

    Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg) appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg. PMID:24348379

  17. Synergistic Effect of Sodium Butyrate and Thalidomide in the Induction of Fetal Hemoglobin Expression in Erythroid Progenitors Derived from Cord Blood CD133 + Cells

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    Ali Dehghanifard

    2012-07-01

    Full Text Available Background: The use of drugs with the ability to induce production of fetal hemoglobin as a novel therapeutic approach in treating β-Hemoglobinopathies is considered. γ-globin gene expression inducer drugs including sodium butyrate and thalidomide can reduce additional α-globin chains accumulation in erythroid precursors. Materials and Methods: In this experimental study, MACS kit was used to isolate CD133+ cells of umbilical cord blood. Further, the effect of two drugs of thalidomide and sodium butyrate were separately and combined studied on the induction of quantitative expression of β-globin and γ-globin genes in erythroid precursor cells derived from CD133+ stem cells in-vitro. For this purpose, the technique SYBR green Real-time PCR was used.Results: Flow cytometry results showed that approximately 95% of purified cells were CD133+. Real-time PCR results also showed the increased levels of γ-globin mRNA in the cell groups treated with thalidomide, sodium butyrate and combination of drugs as 2.6 and 1.2 and 3.5 times respectively, and for β-globin gene, it is respectively 1.4 and 1.3 and 1.6 times compared with the control group (p<0.05.Conclusion: The study results showed that the mentioned drug combination can act as a pharmaceutical composition affecting the induction of fetal hemoglobin expression in erythroid precursor cells derived from CD133 + cells.

  18. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; Granell, Miguel; Oriol, Albert; Martinez-Lopez, Joaquin; Blade, Joan; Hernandez, Miguel T; Martín, Jesus; Gironella, Mercedes; Lynch, Mark; Bleickardt, Eric; Paliwal, Prashni; Singhal, Anil; San-Miguel, Jesus

    2016-11-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM. © 2016 John Wiley & Sons Ltd.

  19. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma.

    NARCIS (Netherlands)

    Lokhorst, H.M.; Schmidt-Wolf, I.; Sonneveld, P.; Holt, B. van der; Martin, H.; Barge, R.; Bertsch, U.; Schlenzka, J.; Bos, G.M.; Croockewit, S.; Zweegman, S.; Breitkreutz, I.; Joosten, P.; Scheid, C.; Marwijk-Kooy, M. van; Salwender, H.J.; Oers, M.H. van; Schaafsma, R.; Naumann, R.; Sinnige, H.A.M.; Blau, I.; Delforge, M.; Weerdt, O. de; Wijermans, P.W.; Wittebol, S.; Duersen, U.; Vellenga, E.; Goldschmidt, H.

    2008-01-01

    In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001).

  20. Indeterminate cell histiocytosis in a pediatric patient: successful treatment with thalidomide.

    Science.gov (United States)

    Tóth, Béla; Katona, Mária; Hársing, Judit; Szepesi, Agota; Kárpáti, Sarolta

    2012-04-01

    The 15-year-old male patient presented several 2-6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.

  1. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay

    2004-10-01

    Full Text Available A talidomida, descoberta na Alemanha Oriental, em 1954, mostrou vários efeitos terapêuticos: antiemético, sedativo e hipnótico. De 1959 a 1961, foram descritas cerca de 12.000 crianças nascidas com defeitos teratogênicos. Seu uso foi, conseqüentemente, suspenso. Sheskin, entretanto, recomeçou a usar a droga e verificou efeito benéfico no eritema nodoso leprótico. A talidomida é derivada do ácido glutâmico. Sua eliminação urinária é mínima (1%. Tem ações: antiinflamatória, imunomoduladora e antiangiogênica. Tem sido usada, com certo êxito terapêutico, em algumas entidades mais adiante estudadas. O principal efeito adverso é teratogênico: alterações nos membros, orelhas, olhos e órgãos internos. Supõe-se que esses efeitos teratogênicos decorram da ação antiangiogênica. Outros efeitos adversos: cefaléia, secura da pele e da mucosa da boca, prurido, erupção cutânea, aumento de peso, hipotireoidismo, neutropenia, bradicardia ou taquicardia e hipotensão. Interage com outros fármacos: barbitúrico, clorpromazina, reserpina, álcool, acetaminofen, histamina, serotonina e prostaglandina.Thalidomide was discovered in East Germany in 1954. It presented with several therapeutic effects: antiemetic, sedative and hypnotic. From 1959 to 1961, roughly 12,000 children born with teratogenic defects were described. Its use was consequently halted. Sheskin started using the drug again and observed its beneficial effect on erythema nodosa leprosum. Thalidomide is derived from glutamic acid. Its urinary elimination is minimal (1%. It has the following actions: anti-inflammatory, immunomodulary and antiangiogenic. It has been used with a successful therapeutic outcome on some entities, which have been studied further. The main side effect is teratogenic: limb alterations, ears, eyes and internal organs. The teratogenic effects are assumed to result from antiangiogenic action. Other side effects are cephalea, dry skin and mouth

  2. HELLP syndrome is associated with an increased inflammatory response, which may be inhibited by administration of prednisolone

    NARCIS (Netherlands)

    Heimel, Pieter J. van Runnard; Kavelaars, Annemiek; Heijnen, Cobie J.; Peters, Wilbert H. M.; Huisjes, Anjoke J. M.; Franx, Arie; Bruinse, Hein W.

    2008-01-01

    Objective. To investigate the effect of prednisolone on HELLP syndrome by assessing several markers of the inflammatory response and hepatic damage associated with HELLP syndrome. Design. Prospective study. Setting. Single-center, tertiary obstetric care facility at the University Medical Centre

  3. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  4. Association between desloratadine and prednisolone in the treatment of children with acute symptoms of allergic rhinitis: a double-blind, randomized and controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Gustavo F. Wandalsen

    Full Text Available Abstract Introduction: A combination of antihistamines and oral corticosteroids is often used to treat acute symptoms of allergic rhinitis. Objective: To evaluate safety and efficacy of desloratadine plus prednisolone in the treatment of acute symptoms of children (2-12 years with allergic rhinitis, and to compare it to dexchlorpheniramine plus betamethasone. Methods: Children with moderate/severe persistent allergic rhinitis and symptomatic (nasal symptoms score [0-12] ≥ 6 were allocated in a double-blind, randomized fashion to receive dexchlorpheniramine plus betamethasone (n = 105; three daily doses or desloratadine plus prednisolone (n = 105; single dose followed by two of placebo for 7 days. At the beginning and end of the evaluation, the following were obtained: nasal symptoms score, extra nasal symptoms score, peak nasal inspiratory flow, blood biochemistry, and electrocardiogram. Ninety-six children of the dexchlorpheniramine plus betamethasone group and 98 of the desloratadine plus prednisolone group completed the protocol. Results: The two groups were similar regarding initial and final nasal symptoms scores, extra nasal symptoms scores and peak nasal inspiratory flow. A drop of 76.4% and 79.1% for nasal symptoms score, 86.0% and 79.2% for extra nasal symptoms score, as well as an increase of 25.2% and 24.3% for peak nasal inspiratory flow occurred for those treated with desloratadine plus prednisolone and dexchlorpheniramine plus betamethasone, respectively. There were no significant changes in blood chemistry. Sinus tachycardia was the most frequent electrocardiogram change, but with no clinical significance. Drowsiness was reported significantly more often among those of dexchlorpheniramine plus betamethasone group (17.14% × 8.57%, respectively. Conclusion: The desloratadine plus prednisolone combination was able to effectively control acute symptoms of rhinitis in children, improving symptoms and nasal function. Compared to the

  5. Molecular and cellular mechanisms of vitamin D3 protection in experimental prednisolone-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    I.O. Shymanskyi

    2017-08-01

    Full Text Available Background. Osteoporosis is the most common side effect of glucocorticoid (GC therapy. Vitamin D is known to play a crucial role in bone remodeling, but the precise molecular mechanisms of its action on GC-induced impairments of cytokine systems, in particular RANK (receptor activator of nuclear factor kappa-B/RANKL (RANK ligand/OPG (osteoprotegerin, are still controversial. Thus, the purpose of the study was to evaluate GC-induced changes in the RANK/RANKL/OPG system and osteocalcin synthesis in rat bone depending on vitamin D bioavailability and vitamin D receptor (VDR expression. Materials and methods. Female Wistar rats received prednisolone (5 mg/kg b.w. with or without 100 IU of vitamin D3 (for 30 days. The levels of VDR, osteocalcin, RANK, RANKL and OPG in bone tissue were determined by western blotting. Blood serum 25OHD was assayed by enzyme-linked immunosorbent assay. The levels of Ca2+, Pi, activity of alkaline phosphatase (AP and its bone isoenzyme were determined using spectrophotometry. Results. Prednisolone significantly lowered 25OHD content in the blood serum and VDR level in bone tissue that has been accompanied by an elevation of the AP bone isoenzyme activity in the blood serum, hypocalcemia and hypophosphatemia. A significant decrease in the expression of osteocalcin, a well-known marker of bone formation, was also observed. GC-induced disturbances in vitamin D status led to a reduction of the RANK and OPG level, while RANKL level was unaffected. Vitamin D3 administration restored 25OHD and VDR levels that resulted in amelioration of GC-induced changes in bone tissue and normalization of mineral metabolism through elevation of RANK, OPG and osteocalcin levels. Conclusions. Prednisolone-induced imbalance in the RANK/RANKL/OPG and osteocalcin systems is related to the reduction of vitamin D bioavailability and impairments in VDR signaling. Thus, normalization of vitamin D bioavailability might be perspective in reducing the

  6. Pressurized Anneal of Consolidated Powders

    Science.gov (United States)

    Nemir, David Charles (Inventor); Rubio, Edward S. (Inventor); Beck, Jan Bastian (Inventor)

    2017-01-01

    Systems and methods for producing a dense, well bonded solid material from a powder may include consolidating the powder utilizing any suitable consolidation method, such as explosive shockwave consolidation. The systems and methods may also include a post-processing thermal treatment that exploits a mismatch between the coefficients of thermal expansion between the consolidated material and the container. Due to the mismatch in the coefficients, internal pressure on the consolidated material during the heat treatment may be increased.

  7. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study

    NARCIS (Netherlands)

    Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Vincent, Andrew D.; Korse, Catharina M.; van Klaveren, Rob J.; Schramel, Franz M. N. H.; Pavlakis, Nick; Nowak, Anna K.; Custers, Frank L. J.; Schouwink, J. Hugo; Gans, Steven J. M.; Groen, Harry J. M.; Strankinga, Wim F. M.; Baas, Paul

    2013-01-01

    Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic

  8. Does perioperative high-dose prednisolone have clinical benefits for generalized myasthenia gravis?

    Science.gov (United States)

    Sekine, Yasuo; Kawaguchi, Naoki; Hamada, Chikuma; Sekiguchi, Hiromi; Yasufuku, Kazuhiro; Iyoda, Akira; Shibuya, Kiyoshi; Fujisawa, Takehiko

    2006-06-01

    The purpose of this study was to clarify the clinical benefits of perioperative administration of high-dose prednisolone (PSL) combined with extended thymectomy on the long-term outcomes of 116 consecutive patients with generalized myasthenia gravis (MG). A retrospective review was conducted on 116 patients diagnosed with generalized MG who received alternate-day oral administration of high-dose PSL (100 mg/alternate days) and had undergone transsternal extended thymectomy. Incidences of postoperative myasthenic crisis, adverse effects of steroid, long-term outcomes, such as complete stable remission (CSR), pharmacologic remission (PR) or improvement (Imp), and disease recurrence after CSR were evaluated. Six patients (5.2%) experienced post-thymectomy myasthenic crisis. Crude cumulative CSR and PR + CSR rates were 44.8 and 62.7%, respectively. Life table analysis showed that 41.8, 52.8 and 63.4% of the patients were in CSR at 3, 5 and 10 years, respectively. Multivariate analysis revealed that age and pretreatment classification according to the Myasthenia Gravis Foundation of America (MGFA) criteria tended to be independent predictors of CSR. There were 6.9% with compressive vertebral fracture, 13.8% with cataract, and 5.2% with steroid-induced diabetes. Life table analysis revealed that recurrence rates after CSR were 36.8 and 46.0% at 3 and 5 years, respectively. Patients with thymoma had a significantly higher rate of recurrence than those without thymoma (p = 0.001). Alternate-day administration of high-dose prednisolone reduced the risk of post-thymectomy myasthenic crisis. Presence of thymoma was a risk factor for MG recurrence after CSR.

  9. Knogletab under lavdosis-glukokortikoidbehandling hos patienter med polymyalgia rheumatica. En dobbeltblind, prospektiv sammenligning mellem prednisolon og deflazacort

    DEFF Research Database (Denmark)

    Krogsgaard, M R; Thamsborg, G; Lund, B

    1997-01-01

    or deflazacort. Bone Mineral Content (BMC) was measured in the lumbar spine (L-BMC) and distal forearm (A-BMC) before treatment and three, six and 12 months after the start of treatment. After three months the decrease in L-BMC was significantly greater in the deflazacort group than in the prednisolone group (p...

  10. Real-time measurement of blood pressure with Nexfin in a patient with thalidomide-related phocomelia.

    Science.gov (United States)

    Earle, Rosie; Vaghadia, Himat; Shanahan, Enda; Tang, Raymond; Sawka, Andrew

    2016-11-01

    We report the novel application of photoplethysmographic technology with the Nexfin HD monitor for real-time measurement of blood pressure (BP) in a patient with tetraamelia. The patient was a 58-year-old man with tetraamelia secondary to thalidomide exposure in utero, who presented for surgical excision of a maxillary schwannoma. Because difficulty of cuff use on rudimentary limbs and failure to gain invasive arterial access due to abnormalities of limb vasculature, this population is known to pose some unique challenges for BP measurement. Nexfin may offer an alternative noninvasive method to detect BP in patients with phocomelia during the perioperative period. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Induction of Severe Chronic Hyperplastic Candidiasis in Rat by Opportunistic Infection of C. albicans through Combination of Diabetes and Intermittent Prednisolone Administration.

    Science.gov (United States)

    Terayama, Yui; Matsuura, Tetsuro; Ozaki, Kiyokazu

    2017-08-01

    Chronic hyperplastic candidiasis progresses from squamous cell hyperplasia to squamous cell carcinoma (SCC); however, the oncogenic mechanism remains unclear. In the present study, we attempted to induce opportunistic Candida albicans infection and establish chronic hyperplastic candidiasis in rats by combining diabetic condition and prednisolone administration, followed by analysis of the inflammatory cells involved in the disease progression. Female Wistar Bunn/Kobori (WBN/Kob) rats were divided into 3 groups: alloxan-induced diabetic rats (A group) along with diabetic (AP group) and nondiabetic (P group) rats intermittently treated with prednisolone. Animals were euthanized at 42 weeks of age. Squamous cell hyperplasia following C. albicans infection in the forestomach was observed in almost all AP and A group rats. The lesions in the AP group were significantly more severe than those in the A group. In addition, SCC was detected in 1 AP group animal. Cluster of differentiation (CD)4-positive T cell and CD68-positive macrophage infiltration in the AP group was significantly stronger than that in the A group. These findings suggest that the combination of diabetes and intermittent prednisolone administration could induce chronic hyperplastic candidiasis without direct C. albicans inoculation and that CD4-positive T cells and CD68-positive macrophages may be highly involved in the pathogenesis of these hyperplastic lesions.

  12. 75 FR 32555 - Consolidated Audit Trail

    Science.gov (United States)

    2010-06-08

    ... Part II Securities and Exchange Commission 17 CFR Part 242 Consolidated Audit Trail; Proposed Rule... 3235-AK51 Consolidated Audit Trail AGENCY: Securities and Exchange Commission. ACTION: Proposed rule... a consolidated order tracking system, or consolidated audit trail, with respect to the trading of...

  13. Dry rod consolidation technology development

    International Nuclear Information System (INIS)

    Rasmussen, T.L.; Schoonen, D.H.; Feldman, E.M.; Fisher, M.W.

    1987-01-01

    The Department of Energy's (DOE) Office of Civilian Radioactive Waste Management (OCRWM) is funding a program to consolidate commercial spent fuel for testing in dry storage casks and to develop technology that will be fed into other OCRWM programs, e.g., Prototypical Consolidation Demonstration Program (PCDP). The program is being conducted at the Idaho National Engineering Laboratory (INEL) by the INEL Operating Contractor EG and G Idaho, Inc. Hardware and software have been designed and fabricated for installation in a hot cell adjacent to the Test Area North (TAN) Hot Shop Facility. This equipment is used to perform dry consolidation of commercial spent fuel from the Virginia Power (VP) Cooperative Agreement Spent Fuel Storage Cask (SFSC) Demonstration Program and assemblies that had previously been stored at the Engine Maintenance and Disassembly (EMAD) facility in Nevada. Consolidation is accomplished by individual, horizontal rod pulling. A computerized semiautomatic control system with operator involvement is utilized to conduct consolidation operations. During consolidation operations, data is taken to characterize this technology. Still photo, video tape, and other documentation will be generated to make developed information available to interested parties. Cold checkout of the hardware and software was completed in September of 1986. Following installation in the hot cell, consolidation operations begins in May 1987. Resulting consolidated fuel will be utilized in the VP Cooperative Agreement SFSC Program

  14. Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection

    DEFF Research Database (Denmark)

    Bélard, Erika; Semb, Synne; Ruhwald, Morten

    2011-01-01

    (TST). METHODS: A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohn's disease (54), rheumatoid arthritis (111), and spondylo-arthropathy (44). RESULTS: QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54....../238 (23%) patients. Chest x-ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had =1 risk-factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment. During prednisolone.......0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1-0.8; P = 0.018), and with an increased risk of indeterminate QFT-IT results AOR 16.1 (4.1-63.2; P negative effect was found for long...

  15. Dry rod consolidation technology development

    International Nuclear Information System (INIS)

    Rasmussen, T.L.; Schoonen, D.H.; Fisher, M.W.

    1986-01-01

    The Department of Energy's (DOE) Office of Civilian Radioactive Waste Management (OCRWM) is funding a Program to consolidate commercial spent fuel for testing in dry storage casks and to develop technology that will be fed into other OCRWM Programs, e.g., Prototypical Consolidation Demonstration Program. The Program is being conducted at the Idaho National Engineering Laboratory (INEL) by the Operating Contractor, EGandG Idaho, Inc. Hardware and software have been designed and fabricated for installation in a hot cell adjacent to the Test Area North (TAN) Hot Shop Facility. This equipment will be used to perform dry consolidation of commercial spent fuel from the Virginia Power (VP) Cooperative Agreement Spent Fuel Storage Cask (SPSC) Demonstration Program and assemblies that had previously been stored at the Engine Maintenance and Disassembly (EMAD) facility in Nevada. Consolidation will be accomplished by individual, horizontal rod pulling. A computerized semi-automatic control system with operator involvement will be utilized to conduct consolidation operations. Special features have been incorporated in the design to allow crud collection and measurement of rod pulling forces. During consolidation operations, data will be taken to characterize this technology. Still photo, video tape, and other documentation will be generated to make developed information available to interested parties. Cold checkout of the hardware and software will complete in September of 1986. Following installation in the hot cell, consolidation operations will begin in January 1987. Resulting consolidated fuel will be utilized in the VP Cooperative Agreement SFSC Program

  16. Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells

    Directory of Open Access Journals (Sweden)

    Madácsi Ramóna

    2010-06-01

    Full Text Available Abstract Background Cytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides with potent anticancer activities were synthesized. Results Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER, induction of reactive oxygen species (ROS, ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis. Conclusions Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

  17. 7 CFR 283.16 - Consolidation of issues.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Consolidation of issues. 283.16 Section 283.16... Claims of $50,000 or More § 283.16 Consolidation of issues. Similar issues involved in appeals by two or...) Disposition of consolidated issues. If the ALJ orders consolidation, the issues consolidated will be...

  18. Osmotic consolidation of suspensions and gels

    International Nuclear Information System (INIS)

    Miller, K.T.; Zukoski, C.F.

    1994-01-01

    An osmotic method for the consolidation of suspensions of ceramic particles is demonstrated. Concentrated solutions of poly(ethylene oxide) are separated from a suspension of ceramic particles by a semipermeable membrane, creating a gradient in solvent chemical potential. Solvent passes from the suspension into the polymer solution, lowering its free energy and consolidating the suspension. Dispersions of stable 8-nm hydrous zirconia particles were consolidated to over 47% by volume. Suspensions of α-alumina in three states of aggregation (dispersed, weakly flocculated, and strongly flocculated) were consolidated to densities greater than or equal to those produced in conventional pressure filtration. Moreover, the as-consolidated alumina bodies were partially drained of fluid during the osmotic consolidation process, producing cohesive partially dried bodies with improved handling characteristics

  19. Consolidation of tailings

    International Nuclear Information System (INIS)

    Nelson, J.D.; Wardwell, R.E.; Abt, S.R.; Staub, W.P.

    1983-09-01

    The integrity of cover systems placed on tailings impoundments will be affected by the potential for differential settlement of the tailings surface. Settlement of the sand fraction will occur relatively rapidly. The slimes will take longer time for consolidation and will produce greater settlement. This report reviews the phenomenon of consolidation for saturated and unsaturated tailings. The effect of load application by cover placement and the extent to which dewatering of tailings will cause consolidation are considered. In addition, the feasibility of inducing consolidation by alternative means and the potential applicability of these methods to tailings impoundments reclamation are discussed. Differential settlement of the tailings will cause tensile strain to be developed in covers. This strain could be large enough to cause cracking within a relatively brittle compacted clay. Dewatering of tailings by drainage can cause settlement even greater than that by placement of a cover material. Dewatering of the tailings would also increase the stability of the tailings surface, thereby enhancing reclamation operations. Consequently, in view of the enhanced surface stability and the fact that a portion of the differential settlement can be accomplished prior to cover placement, dewatering of tailings impoundments during operations may have benefical effects

  20. ¿Por qué se está usando otra vez la talidomida? Why is thalidomide back?

    Directory of Open Access Journals (Sweden)

    Emilio Sanín Pérez

    2004-02-01

    óxica ni en la Enfermedad crónica injerto contra huésped. Background: in 1998 the FDA approved the restricted commercialization of Thalidomide for the treatment of Erithema Nodosum Leprosum. Brazil and Mexico have also regulated its use. Because of the current use of this teratogenic drug in rheumatological, dermatological, infectious and neoplasic diseases, it is necessary to instruct General Practitioners and specialists on its most relevant topics, active principle, benefic and deleterious effects. We carried out a revision by reading and analyzing controlled clinical trials, randomized or not, case series and reviews about thalidomide and its potential uses, that appeared in Medline from January 1993 to December 2003, to draw indications and contraindications in light of the evidence found in them. Results: forty six randomized controlled studies were found and 22 (with at least 50 patients described were reviewed (complete articles and/or including design and end points measured – expressed abstracts, plus 10 reviews and 22 cases series. The analysis allowed us to inform potential or restricted and not indicated uses of thalidomide in humans, its pharmacokynetic principles which explain its benefic and deleterious effects, and recommendations to prevent teratogenesis. Conclusion: thalidomide is available, with restrictions, for the treatment of Erithema Nodosum Leprosum (first line and Multiple Myeloma (refractory to multiple chemotherapy. It appears to have beneficial effects in many other serious conditions refractory to first line treatments: AIDS, esophagus and prostate cancer and some severe dermatosis, rheumatological or not.

  1. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study.

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Catherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2015-11-01

    Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy. We recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. Between Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15·9 months (IQR 10·1-22·3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74-98) patients had partial responses

  2. EDF - 2005 Consolidated Annual Results - Analysts' Presentation. Consolidated financial statements at December 31, 2005

    International Nuclear Information System (INIS)

    2006-01-01

    As the world's biggest electricity generator, the EDF Group covers every sector of expertise, from generation to trading and transmission grids. EDF builds on the expertise of its people, its R and D and engineering skills, its experience as a leading industry operator and the attentive support of its customers to deliver competitive solutions that successfully reconcile economic growth with climate protection. This document presents the 2005 annual results and Consolidated financial statements of the Group at 31 December 2005: Consolidated income statements, consolidated balance sheets, consolidated cash flow statements, variation in consolidated equity, notes (group accounting policies, impact of first-time application of IFRs, transition to standards IAS 32 and 39 concerning financial instruments, summary of accounting and valuation methods, public distribution concessions in France, significant events and transactions of 2005, impact of the law of august 9, 2004 on comparability, changes in the scope of consolidation, segment reporting, sales, fuel and energy purchases, other external expenses, contractual obligations and commitments entered into in the course of business, personnel expenses, other operating income and expenses, other income and expenses, financial result, income taxes, basic earnings per share and diluted earnings per share, goodwill, other intangible assets, property, plant and equipment, investments in companies accounted for under the equity method, financial assets, inventories, including work-in-process, trade receivables, other receivables, cash and cash equivalents, available-for-sale assets and liabilities, equity, provisions, special concession liabilities, current and non-current financial liabilities, derivatives, other liabilities, related parties, greenhouse gas emission quotas, environment, subsequent events, scope of consolidation

  3. Efficacy and safety of a 3-month loteprednol etabonate 0.5% gel taper for routine prophylaxis after photorefractive keratectomy compared to a 3-month prednisolone acetate 1% and fluorometholone 0.1% taper

    Directory of Open Access Journals (Sweden)

    Mifflin MD

    2017-06-01

    Full Text Available Mark D Mifflin,1 Brent S Betts,1 P Adam Frederick,2 Jason M Feuerman,3 Carlton R Fenzl,4 Majid Moshirfar,1,5 Brian Zaugg1 1Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT, 2The Eye Center, Huntsville, AL, 3Eye Institute of Austin, Austin, TX, 4Eye Surgeons Associates, Bettendorf, IA, 5Hoopes Vision, Draper, UT, USA Purpose: To compare the outcome of photorefractive keratectomy (PRK and complications in patients treated with either loteprednol etabonate 0.5% gel or prednisolone acetate 1% suspension and fluorometholone (fml 0.1% suspension.Setting: John A Moran Eye Center, University of Utah, Salt Lake City, UT, USA.Design: Prospective, randomized, partially masked trial.Methods: PRK was performed on 261 eyes of 132 participants. Patients were randomized to a postoperative corticosteroid regimen of either loteprednol etabonate 0.5% gel (loteprednol or prednisolone 1% acetate suspension followed by fluorometholone 0.1% suspension (prednisolone/fml. Primary outcome measures included incidence and grade of postoperative corneal haze and incidence of increased intraocular pressure of 10 mmHg above baseline, or any intraocular pressure over 21 mmHg. Secondary outcome measures included uncorrected distance visual acuity, best corrected distance visual acuity, and manifest refraction spherical equivalent.Results: The incidence of haze in the first 3 months was 2.6% (3/114 eyes in the loteprednol group and 4.8% (7/147 eyes in the prednisolone/fml group and was not statistically significant between groups (P=0.37. The incidence of elevated intraocular pressure was 1.8% (2/114 eyes in the loteprednol group and 4.1% (6/147 eyes in the prednisolone/fml group, and was not statistically significant between the groups (P=0.12. The mean 3-month postoperative logMAR uncorrected visual acuity was −0.078±0.10 and −0.075±0.09 in the loteprednol and prednisolone/fml groups, respectively (P=0

  4. A biomechanical, micro-computertomographic and histological analysis of the influence of diclofenac and prednisolone on fracture healing in vivo.

    Science.gov (United States)

    Bissinger, Oliver; Kreutzer, Kilian; Götz, Carolin; Hapfelmeier, Alexander; Pautke, Christoph; Vogt, Stephan; Wexel, Gabriele; Wolff, Klaus-Dietrich; Tischer, Thomas; Prodinger, Peter Michael

    2016-09-05

    Non-steroidal anti-inflammatory drugs (NSAIDs) have long been suspected of negatively affecting fracture healing, although numerous disputes still exist and little data are available regarding diclofenac. Glucocorticoids interfere in this process over a similar and even broader mechanism of action. As many previously conducted studies evaluated either morphological changes or biomechanical properties of treated bones, the conjunction of both structural measures is completely missing. Therefore, it was our aim to evaluate the effects of diclofenac and prednisolone on the fracture callus biomechanically, morphologically and by 3-dimensional (3D) microstructural analysis. Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (μCT) and histology were examined. The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and μCT (e.g. stiffness: 57.31 ± 31.11 N/mm vs. 122.44 ± 81.16 N/mm, p = 0.030; callus volume: 47.05 ± 15.67 mm3 vs. 67.19 ± 14.90 mm3, p = 0.037, trabecular thickness: 0.0937 mm ± 0.003 vs. 0.0983 mm ± 0.003, p = 0.023), as confirmed by histology. Biomechanics of the prednisolone group showed obviously lower absolute values than the control group. These alterations were confirmed in conjunction with μCT and histology. The inhibiting effects of both substances were not only mediated by absolute parameters (e.g. breaking load, BV), but we have shown, for the first time, that additional changes occurred in the microstructural bony network. Especially in patients at risk for delayed bone healing (arteriosclerosis, diabetes mellitus, smoking), the administration of these drugs should be weighed carefully.

  5. Distribution center consolidation games

    NARCIS (Netherlands)

    Klijn, F.; Slikker, M.

    2005-01-01

    We study a location-inventory model to analyze the impact of consolidation of distribution centers on facility and inventory costs. We introduce a cooperative game and show that when demand processes are i.i.d. the core is non-empty, i.e., consolidation allows for a stable division of the minimal

  6. 77 FR 45721 - Consolidated Audit Trail

    Science.gov (United States)

    2012-08-01

    ... maintain a consolidated order tracking system, or consolidated audit trail, with respect to the trading of... With a Consolidated Audit Trail 3. Large Trader Reporting System Rule B. Summary of Proposed Rule 613 C... Authority (``FINRA'') and some of the exchanges currently maintain their own separate audit trail systems...

  7. 26 CFR 1.1502-3 - Consolidated tax credits.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated tax credits. 1.1502-3 Section 1... (CONTINUED) INCOME TAXES Consolidated Tax Liability § 1.1502-3 Consolidated tax credits. (a) Determination of...) Consolidated limitation based on amount of tax. (i) Notwithstanding the amount of the consolidated credit...

  8. LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.

    Science.gov (United States)

    Shu, Chang; Zeng, Tianmei; Gao, Shouhong; Xia, Tianyi; Huang, Lifeng; Zhang, Feng; Chen, Wansheng

    2016-08-15

    Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Consolidity: Mystery of inner property of systems uncovered

    Directory of Open Access Journals (Sweden)

    Hassen T. Dorrah

    2012-10-01

    Full Text Available This paper uncovers the mystery of consolidity, an inner property of systems that was amazingly hidden. Consolidity also reveals the secrecy of why strong stable and highly controllable systems are not invulnerable of falling and collapsing. Consolidity is measured by its Consolidity Index, defined as the ratio of overall changes of output parameters over combined changes of input and system parameters, all operating in fully fuzzy environment. Under this notion, systems are classified into consolidated, quasi-consolidated, neutrally consolidated, unconsolidated, quasi-unconsolidated and mixed types. The strategy for the implementation of consolidity is elaborated for both natural and man-made existing systems as well as the new developed ones. An important critique arises that the by-product consolidity of natural or built-as-usual system could lead to trapping such systems into a completely undesired unconsolidity. This suggests that the ample number of conventional techniques that do not take system consolidity into account should gradually be changed, and adjusted with improved consolidity-based techniques. Four Golden Rules are highlighted for handling system consolidity, and applied to several illustrative case studies. These case studies cover the consolidity analysis of the Drug Concentration problem, Predator-Prey Population problem, Spread of Infectious Disease problem, AIDS Epidemic problem and Arm Race model. It is demonstrated that consolidity changes are contrary (opposite in sign to changes of both stability and controllability. This is a very significant result showing that our present practice of stressing on building strong stable and highly controllable systems could have already jeopardized the consolidity behavior of an ample family of existing real life systems. It is strongly recommended that the four Golden Rules of consolidity should be enforced as future strict regulations of systems modeling, analysis, design and

  10. Dry Rod Consolidation Technology Project results

    International Nuclear Information System (INIS)

    Mullen, C.K.; Feldman, E.M; Vinjamuri, K.; Griebenow, B.L.; Lynch, R.J.; Arave, A.E.; Hill, R.C.

    1988-01-01

    The Dry Rod Consolidation Technology (DRCT) Project conducted at the Idaho National Engineering Laboratory (INEL), in 1987 demonstrated the technical feasibility of a dry horizontal fuel rod consolidation process. Fuel rods from Westinghouse 15 /times/ 15 pressurized water reactor (PWR) spent fuel assemblies were consolidated into canisters to achieve a 2:1 volume reduction ratio. The consolidation equipment was operated at an existing hot cell complex at the INEL. The equipment was specifically designed to interface with the existing facility fuel handling and operational capabilities and was instrumented to provide data collection for process technology research. During the operational phase, data were collected from observation of the consolidation process, fuel assembly handling, and fuel rod behavior and characteristics. Equipment performance was recorded and data measurements were compiled on crud and contamination generated and spread. Fuel assembly skeletons [non-fuel bearing components (NFBC)] were gamma scanned and analyzed for isotopic content and profile. The above data collection was enhanced by extensive photograph and video documentation. The loaded consolidation fuel canisters were utilized for a test of the Transnuclear, Inc. TN-24P dry storage cask with consolidated fuel. The NFBC material was stored for a future volume reduction demonstration project. 14 figs., 4 tabs

  11. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  12. Is autism partly a consolidation disorder?

    Science.gov (United States)

    Femia, Lisa A; Hasselmo, Michael E

    2002-12-01

    Computational modeling has been useful for understanding processes of encoding and consolidation in cortical structures. In particular, this work suggests a role of neuromodulators in setting dynamics for consolidation processes during different stages of waking and sleep. Because autistic individuals show symptoms of a cognitive nature coupled with a high prevalence of comorbid conditions such as epileptiform discharge during sleep and sleep disorders, it is possible that autism could involve a breakdown in consolidation processes, which are essential to build effective cognitive representations of the environment on the basis of individual experiences. In this article, theories of consolidation during different stages of waking and sleep and the role of different neuromodulators in these consolidation processes are reviewed in conjunction with different features of autism, which may be understood in the context of these theories.

  13. Consolidation and Disclosure of SPE

    OpenAIRE

    中野, 貴之

    2011-01-01

    The purpose of this study is to discuss what kinds of information are demanded by the users of financial statements and what kinds of problems plague the companies using SPE (special purpose equity), while considering the actual situations of the consolidation and disclosure of SPE in Japan. At present, there is the trend of consolidating a broad range of SPE in Japan, etc., but some users of financial statements point out that it became difficult to understand consolidated financial stat...

  14. FEATURES OF CONSOLIDATED FINANCIAL STATEMENTS: FOREIGN EXPERIENCE

    Directory of Open Access Journals (Sweden)

    S. V. KUCHER

    2016-12-01

    Full Text Available The article researches the features of preparation and submission of the consolidated financial statements of the world countries of different systems of accounting standardization in order to identify the areas of accounting improvement for the process of consolidation of financial reporting indicators. The main problems of consolidated financial statements preparation by business entities in Ukraine are determined. The author determines the theoretical and practical problems of consolidation of financial statements of organizational and methodical character. The comparative analysis of the features of standardization process of financial statements consolidation in the world countries is carried out. The main differences in the requirements for the formation of consolidated financial statements indicators of such countries as the French Republic, the Federal Republic of Germany, the Republic of Belarus and the People’s Republic of China are outlined. The main directions of scientific researches on the improvement of accounting and analytical support for the preparation of consolidated financial statements are formed.

  15. Ciclosporin compared with prednisolone therapy for patients with pyoderma gangrenosum: cost-effectiveness analysis of the STOP GAP trial.

    Science.gov (United States)

    Mason, J M; Thomas, K S; Ormerod, A D; Craig, F E; Mitchell, E; Norrie, J; Williams, H C

    2017-12-01

    Pyoderma gangrenosum (PG) is a painful, ulcerating skin disease with poor evidence for management. Prednisolone and ciclosporin are the most commonly used treatments, although not previously compared within a randomized controlled trial (RCT). To compare the cost-effectiveness of ciclosporin and prednisolone-initiated treatment for patients with PG. Quality of life (QoL, EuroQoL five dimensions three level questionnaire, EQ-5D-3L) and resource data were collected as part of the STOP GAP trial: a multicentre, parallel-group, observer-blind RCT. Within-trial analysis used bivariate regression of costs and quality-adjusted life years (QALYs), with multiple imputation of missing data, informing a probabilistic assessment of incremental treatment cost-effectiveness from a health service perspective. In the base case analysis, when compared with prednisolone, ciclosporin was cost-effective due to a reduction in costs [net cost: -£1160; 95% confidence interval (CI) -2991 to 672] and improvement in QoL (net QALYs: 0·055; 95% CI 0·018-0·093). However, this finding appears driven by a minority of patients with large lesions (≥ 20 cm 2 ) (net cost: -£5310; 95% CI -9729 to -891; net QALYs: 0·077; 95% CI 0·004-0·151). The incremental cost-effectiveness of ciclosporin for the majority of patients with smaller lesions was £23 374/QALY, although the estimate is imprecise: the probability of being cost-effective at a willingness-to-pay of £20 000/QALY was 43%. Consistent with the clinical findings of the STOP GAP trial, patients with small lesions should receive treatment guided by the side-effect profiles of the drugs and patient preference - neither strategy is clearly a preferred use of National Health Service resources. However, ciclosporin-initiated treatment may be more cost-effective for patients with large lesions. © 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

  16. Common consolidated corporate tax base: grouping and consolidation

    Directory of Open Access Journals (Sweden)

    Danuše Nerudová

    2012-01-01

    Full Text Available After the ten years of work and discussion of the proposal the European Commission has published the proposal of CCCTB directive on 16th March, 2011. This proposal can be considered as unique, for the European Commission is suggesting totally new system of corporate taxation. The aim of the paper is to research the rules for consolidation and grouping suggested in the proposal of CCCTB directive, to identify the possible conflict situations and to suggest the possible solution. The focuses on the provisions regarding the conditions for consolidation and grouping, comprised in chapter IX, Art. 54–60. In that area has been identified, that even though the provisions seem to be clear, their practical application can in some situations lead to double interpretation, mainly with respect to the fact that individual member states are responsible for the implementation of the directive and also national tax administrators and national courts are going to interpret the provisions of the directive. Therefore even though the fact that suggested system is unique and addresses a lot of problems which are facing companies running business on the internal market, the provisions regarding the consolidation rules and rules for group formatting may still lead not to unified interpretation. In that respect, some of the rules should be more specific in order to ensure unified interpretation.

  17. Consolidation of long-term memory: evidence and alternatives.

    Science.gov (United States)

    Meeter, Martijn; Murre, Jaap M J

    2004-11-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of amnesia, but they have not elucidated how consolidation must be envisaged. Here findings are reviewed that shed light on how consolidation may be implemented in the brain. Moreover, consolidation is contrasted with alternative theories of the Ribot gradient. Consolidation theory, multiple trace theory, and semantization can all handle some findings well but not others. Conclusive evidence for or against consolidation thus remains to be found.

  18. The Impact of Approved Accounting Standard AASB 1024 “Consolidated Accounts” on the Information Included in Consolidated Financial Statements

    OpenAIRE

    Pramuka, Bambang Agus

    1995-01-01

    The intent of consolidated financial statements is to provide meaningful, relevant, useful, and reliable information about the operations of a group of companies. In compliance with AASB 1024 'Consolidated Accounts', and AAS 24 Consolidated Financial Reports', a parent entity now has to include in its consolidated financial statements all controlled entities, regardless of their legal form or the ownership interest held. The new Standard also pr...

  19. Schemas and memory consolidation.

    Science.gov (United States)

    Tse, Dorothy; Langston, Rosamund F; Kakeyama, Masaki; Bethus, Ingrid; Spooner, Patrick A; Wood, Emma R; Witter, Menno P; Morris, Richard G M

    2007-04-06

    Memory encoding occurs rapidly, but the consolidation of memory in the neocortex has long been held to be a more gradual process. We now report, however, that systems consolidation can occur extremely quickly if an associative "schema" into which new information is incorporated has previously been created. In experiments using a hippocampal-dependent paired-associate task for rats, the memory of flavor-place associations became persistent over time as a putative neocortical schema gradually developed. New traces, trained for only one trial, then became assimilated and rapidly hippocampal-independent. Schemas also played a causal role in the creation of lasting associative memory representations during one-trial learning. The concept of neocortical schemas may unite psychological accounts of knowledge structures with neurobiological theories of systems memory consolidation.

  20. Fuel consolidation and compaction and storage of NFBC

    International Nuclear Information System (INIS)

    Fuierer, T.

    1992-01-01

    Rochester Gas and Electric Corporation (RG ampersand E) has been involved in two separate fuel consolidation demonstration programs. One of those programs resulted in identifying some problems that may be resolved in consolidation hardware compaction and storage in order for consolidation to be attractive. In conjunction with the Electric Power Research Institute (EPRI), a study was recently performed on hardware compaction and storage. Consolidation is probably not a commercial alternative at this point in time because there are still several problems that must be resolved. There are some potential advantages of fuel consolidation. Consolidation has attractive economics and can minimize the institutional impacts of expanding spent fuel storage by internalizing spent fuel storage operations. The licensing effort is fairly simple. Consolidation may be less likely to have public intervention since the storage expansion will occur inside the plant. Consolidation can be subcontracted and the equipment is temporary. It can be used in conjunction with other storage expansion technologies such as dry storage. Fewer dry storage casks would be needed to store consolidated fuel than would be necessary for intact spent fuel

  1. Energy expenditure and body composition in children with Crohn's disease: effect of enteral nutrition and treatment with prednisolone

    OpenAIRE

    Azcue, M; Rashid, M; Griffiths, A; Pencharz, P

    1997-01-01

    Background—Malnutrition and growth retardation are common complications of Crohn's disease in children. The contribution of resting energy expenditure (REE) to malnutrition is unclear. 
Aims—To characterise the REE and body composition in children with Crohn's disease and compare them with normal controls and patients with anorexia nervosa; to compare the effects of prednisolone and enteral nutrition on energy expenditure and body composition. 
Subjects—Twenty four children wit...

  2. Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Prosthetic Aspects

    Science.gov (United States)

    Gilpin, R. E.

    1963-01-01

    The types of prostheses available for treatment of congenital amputations in children, and the assistance in habilitation which can be expected from their use, are described in this communication. The limb deformities in children commonly associated with the drug thalidomide are phocomelia and amelia. Prosthetic treatment of these is difficult, but in almost every case some assistance can be offered. The degree of this assistance will depend to a large extent on (1) the number of limbs involved, (2) the site of the deformity, (3) the intellectual capacity of the child. These factors are evaluated by a clinic team, consisting of a prosthetist, a therapist, a social worker, and a doctor, who acts as the clinical chief. They are also embodied into a prescription for a prosthesis and into a program of management. Subsequently, the clinic team also carry out an assessment of the result. The prosthetist makes available his knowledge of present-day appliances, and assures that the way is left open for use of new, and perhaps revolutionary prostheses, in the future. ImagesFig. 1(a)-1(b)Fig. 2Fig. 3Fig. 4 PMID:13947980

  3. Consolidation Processes: Raiders & Targets in Polish Financial Institutions

    OpenAIRE

    Poteraj, Jarosław

    2004-01-01

    The work consists of five chapters, an annex and an appendix. In the first chapter the author describes the point of consolidation processes, presents: the meaning of consolidation processes, active and institutional aspects of merger execution, gives a classification of the consolidation processes and considers conditions of execution of consolidations processes in the Polish law, The next chapter concerns reasons of consolidation processes. The author describes there in turn: motives of the...

  4. Sand consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Spain, H H

    1965-01-21

    In a sand consolidation method in which there is injected a mixture of resin-forming liquids comprising an aryl-hydroxy low molecular weight compound, a water- soluble aldehyde, and a catalyst, an improvement is claimed which comprises diluting the resin-forming liquids with a diluent and with water so that the yield of the resin is sufficient to consolidate the sand particles with the minimum desirable pressure. The diluent may be mutually soluble in water and in the resin-forming liquids, and does not affect the setting time of the polymer. The aldehyde and the aryl-hydroxy compound may be in ratio of 5:1, and the diluent, methyl alcohol, is present in a ratio of 2:1 with reference to the water.

  5. Benchmarking multi-dimensional large strain consolidation analyses

    International Nuclear Information System (INIS)

    Priestley, D.; Fredlund, M.D.; Van Zyl, D.

    2010-01-01

    Analyzing the consolidation of tailings slurries and dredged fills requires a more extensive formulation than is used for common (small strain) consolidation problems. Large strain consolidation theories have traditionally been limited to 1-D formulations. SoilVision Systems has developed the capacity to analyze large strain consolidation problems in 2 and 3-D. The benchmarking of such formulations is not a trivial task. This paper presents several examples of modeling large strain consolidation in the beta versions of the new software. These examples were taken from the literature and were used to benchmark the large strain formulation used by the new software. The benchmarks reported here are: a comparison to the consolidation software application CONDES0, Townsend's Scenario B and a multi-dimensional analysis of long-term column tests performed on oil sands tailings. All three of these benchmarks were attained using the SVOffice suite. (author)

  6. Status of rod consolidation, 1988

    International Nuclear Information System (INIS)

    Bailey, W.J.

    1989-01-01

    It is estimated that the spent fuel storage pools at some domestic light-water reactors will run out of space before 2003, the year that the US Department of Energy currently predicts it will have a repository available. Of the methods being studied to alleviate the problem, rod consolidation is one of the leading candidates for achieving more efficient use of existing space in spent fuel storage pools. Rod consolidation involves mechanically removing all the fuel rods from the fuel assembly hardware (i.e., the structural components) and placing the fuel rods in a close-packed array in a canister without space grids. A typical goal of rod consolidation systems is to insert the fuel rods from two fuel assemblies into a canister that has the same exterior dimensions as one standard fuel assembly (i.e., to achieve a consolidation or compaction ratio of 2:1) and to compact the nonfuel-bearing structural components from those two fuel assemblies by a factor of 10 to 20. This report provides an overview of the current status of rod consolidation in the United States and a small amount of information on related activities in other countries. 85 refs., 36 figs., 5 tabs

  7. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study.

    Science.gov (United States)

    Rosiñol, Laura; Oriol, Albert; Teruel, Ana Isabel; Hernández, Dolores; López-Jiménez, Javier; de la Rubia, Javier; Granell, Miquel; Besalduch, Joan; Palomera, Luis; González, Yolanda; Etxebeste, María Asunción; Díaz-Mediavilla, Joaquín; Hernández, Miguel T; de Arriba, Felipe; Gutiérrez, Norma C; Martín-Ramos, María Luisa; Cibeira, María Teresa; Mateos, María Victoria; Martínez, Joaquín; Alegre, Adrián; Lahuerta, Juan José; San Miguel, Jesús; Bladé, Joan

    2012-08-23

    The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).

  8. 24 CFR 401.401 - Consolidated Restructuring Plans.

    Science.gov (United States)

    2010-04-01

    ... PROGRAM (MARK-TO-MARKET) Restructuring Plan § 401.401 Consolidated Restructuring Plans. A PAE may request HUD to approve a Consolidated Restructuring Plan that presents an overall strategy for more than one... resources, HUD will not approve any Consolidated Restructuring Plans that have a detrimental effect on...

  9. 7 CFR 1710.108 - Mergers and consolidations.

    Science.gov (United States)

    2010-01-01

    ... operating efficiency and financial soundness. (b) After a merger or consolidation, RUS will give priority... 7 Agriculture 11 2010-01-01 2010-01-01 false Mergers and consolidations. 1710.108 Section 1710.108... and Basic Policies § 1710.108 Mergers and consolidations. (a) RUS encourages its borrowers to consider...

  10. Control of Bank Consolidated Financial Statements Quality

    Directory of Open Access Journals (Sweden)

    Margarita S. Ambarchyan

    2013-01-01

    Full Text Available The author presents the multiple linear regression model of bank consolidated financial statements quality. The article considers six characteristics that can be used to estimate the level of bank consolidated financial statements quality. The multiple linear regression model was developed, using the results of point-based system of consolidated financial statements of thirty European bank and financial groups on the basis of the developed characteristics. The author offers to use the characteristic significance factor in the process of consolidated financial statements appraisal by points. The constructed regression model is checked on accuracy and statistical significance. The model can be used by internal auditors and financial analytics as an instrument for bank and non-bank consolidated financial statements quality control

  11. The Financial Effects of Consolidation.

    Science.gov (United States)

    Streifel, James S.; And Others

    1991-01-01

    Examination of 19 school district consolidations in 10 states, 1980-84, revealed that, of 6 expenditure categories, only administration showed significant savings 3 years after consolidation, when compared to changes in state average costs during that period. Changes in other expenditure categories varied widely among districts. Contains 22…

  12. Interpretation of Consolidation Test on Søvind Marl

    DEFF Research Database (Denmark)

    Grønbech, Gitte Lyng; Ibsen, Lars Bo; Nielsen, Benjaminn Nordahl

    2012-01-01

    The article deals with the interpretation of consolidation test in order to determine the preconsolidation stress; this is done by reviewing different methods. A main point in the article is the interaction between the consolidation and the secondary consolidation strains, and the methods used...... to separate the two strain types. This is in Denmark traditionally done by a √(t)-log(t) description, where the secondary consolidation first starts when the consolidation process is over. This assumption gives an uncertain description of the strain process, since the two processes in reality run...

  13. Guide to Direct Consolidation Loans.

    Science.gov (United States)

    Department of Education, Washington, DC.

    Intended for financial aid counselors, this document provides guidelines to the Federal Direct Consolidation Loan Program for borrowers who are in school, as well as those in repayment, or in default. An introductory section explains the basics of the consolidated loan program, loan categories, and interest rates. Next, standards for borrower…

  14. District Consolidation: Rivals Coming Together

    Science.gov (United States)

    Mart, Dan

    2011-01-01

    District consolidation is a highly emotional process. One key to success is sticking to the facts. In Iowa, school districts facing financial difficulties or enrollment concerns do not have to move directly to consolidation. In many cases, districts begin by developing sharing agreements. These sharing agreements may start with simple sharing of…

  15. The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

    Directory of Open Access Journals (Sweden)

    Jing Lu

    2015-01-01

    Full Text Available The International Staging System (ISS is the most important prognostic system for multiple myeloma (MM. It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p<0.001, and the median progression-free survival (PFS was 30/29.5/25 months (p=0.072, respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.

  16. Prevention of mouse-rat brain xenograft rejection by a combination therapy of cyclosporin A, prednisolone and azathioprine

    DEFF Research Database (Denmark)

    Pedersen, E B; Poulsen, F R; Zimmer, J

    1995-01-01

    Embryonic mouse hippocampal tissue was grafted as tissue blocks to the hippocampal region of adult rats and the effect of two different immunosuppressive treatments compared. Immunosuppression with cyclosporin A, prednisolone and azathioprine or with cyclosporin A alone was compared with placebo....... Transplants in the trimedication group displayed distinct cell and neuropil layers and only minimal cellular infiltration by leukocyte common antigen-expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups were densely infiltrated. The results are discussed in relation to the need...

  17. Familiarity speeds up visual short-term memory consolidation.

    Science.gov (United States)

    Xie, Weizhen; Zhang, Weiwei

    2017-06-01

    Existing long-term memory (LTM) can boost the number of retained representations over a short delay in visual short-term memory (VSTM). However, it is unclear whether and how prior LTM affects the initial process of transforming fragile sensory inputs into durable VSTM representations (i.e., VSTM consolidation). The consolidation speed hypothesis predicts faster consolidation for familiar relative to unfamiliar stimuli. Alternatively, the perceptual boost hypothesis predicts that the advantage in perceptual processing of familiar stimuli should add a constant boost for familiar stimuli during VSTM consolidation. To test these competing hypotheses, the present study examined how the large variance in participants' prior multimedia experience with Pokémon affected VSTM for Pokémon. In Experiment 1, the amount of time allowed for VSTM consolidation was manipulated by presenting consolidation masks at different intervals after the onset of to-be-remembered Pokémon characters. First-generation Pokémon characters that participants were more familiar with were consolidated faster into VSTM as compared with recent-generation Pokémon characters that participants were less familiar with. These effects were absent in participants who were unfamiliar with both generations of Pokémon. Although familiarity also increased the number of retained Pokémon characters when consolidation was uninterrupted but still incomplete due to insufficient encoding time in Experiment 1, this capacity effect was absent in Experiment 2 when consolidation was allowed to complete with sufficient encoding time. Together, these results support the consolidation speed hypothesis over the perceptual boost hypothesis and highlight the importance of assessing experimental effects on both processing and representation aspects of VSTM. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Teaching Consolidations Accounting: An Approach to Easing the Challenge

    Science.gov (United States)

    Murphy, Elizabeth A.; McCarthy, Mark A.

    2010-01-01

    Teaching and learning accounting for consolidations is a challenging endeavor. Students not only need to understand the conceptual underpinnings of the accounting requirements for consolidations, but also must master the complex accounting needed to prepare consolidated financial statements. To add to the challenge, the consolidation process is…

  19. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    Science.gov (United States)

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  20. Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Surgery of Limb Defects

    Science.gov (United States)

    Hall, John E.

    1963-01-01

    The deformities commonly seen in “thalidomide babies” are described. These vary from relatively uncomplicated radial-ray defects to complete phocomelia of all four extremities. It is suggested that the care of these children is best carried out in a clinic accustomed to dealing with juvenile amputee problems. A plea is made for very early fitting of upper-extremity prostheses (at approximately three months of age) in cases of unilateral upper-limb deficiencies. A “bucket” for sitting should be supplied for children with quadrilateral phocomelia to sit in when they reach seven or eight months of age. Children with severe upper-limb malformations will be candidates for some form of externally powered prostheses. ImagesFig. 1a and 1bFig. 2a and 2bFig. 3a and 3bFig. 4a and 4bFig. 5a, b and cFig. 6a and 6bFig. 7Fig. 8Fig. 9a and 9bFig. 10a,bFig. 10c and d PMID:13952105

  1. [Impacts of farmland consolidation on farmland landscape].

    Science.gov (United States)

    Deng, Jinsong; Wang, Ke; Li, Jun; Xu, Junfeng; Shen, Zhangquan; Gao, Yurong

    2006-01-01

    Farmland consolidation is the act of regulating, improving, and comprehensively renovating the structure, quality, and layout of field, water, road, forestry, and village in the countryside in a certain area by means of administration, economy, law, and engineering techniques according to the goal and usage defined by land use planning, so as to improve farmland use rate and its output rate, to increase farmland area, and to achieve better productive, living, and ecological environment. Recently, farmland consolidation has been carried out all over the country, especially in its economy-developed regions. But, unscientific planning and unsuitable farmland consolidation engineering have negative effects on field ecological system. In this paper, based on the technology of GIS and RS, the basic theories and methods of landscape ecology and a compositive grading method were applied to analysis the dynamics of farmland landscape fragmentation in Tongxiang county. The results showed that the farmland landscape fragmentation in this county was strongly affected by consolidation. More attention should be paid to the protection of farmland landscape during consolidation, and to avoid or decrease the negative effects resulted from unscientific planning and unsuitable farmland consolidation engineering.

  2. SOME APECTS REGARDING THE CONSOLIDATED FINANCIAL STATEMENTS

    Directory of Open Access Journals (Sweden)

    Szora Tamas Atila

    2012-12-01

    Full Text Available The study is divided into four parts: in the introduction are presented the theoretical aspects of the consolidated financial statements and the consolidation methods. During the second part are shown the structure rates calculated prior and after the consolidation, and in the third are calculated the financial rates of return and the effective tax rates of fixed assets. The conclusion of this study presents that although the consolidated entity is not a tax, it presents the group effort without the internal flows between entities within the group. In terms of the world scientific research typology used by the authors, it refers to descriptive research, explanatory research and applied research. In terms of the novelties, brought by this study, it is specifically determined, based on the actual database, the evolution of structure indicators, indicators of balance, the financial profitability indicators of corporate companies prior to and after consolidation.

  3. A multicentre phase-II feasibility study evaluating gemcitabine /vinorelbine / prednisolone combination chemotherapy in relapsed / refractory hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Naqi, N.; Ahmad, S.; Shah, I.; Khattak, J.

    2013-01-01

    Objective: To determine the efficacy and toxicity of Gemcitabine, Vinorelbine and Prednisolone (GVP) salvage chemotherapy in relapsed / refractory Hodgkin's Lymphoma (HL). Study Design: A phase-II non-randomized single arm study. Place and Duration of Study: This study was conducted at Combined Military Hospital and Medical College Lahore, Mayo Hospital, King Edward Medical University, Lahore, Allied Hospital, Punjab Medical College, Faisalabad and Combined Military Hospital, Rawalpindi, from January 2007 to December 2007. Methodology: Fifty adult patients with relapsed/refractory HL, adequate marrow reserve, hepatorenal and pulmonary functions, with radiological measurable disease and Karnofsky performance status of 0 - 2 non-candidates for stem cell transplantation, were enrolled. Four 28 days cycles of GVP (Gemcitabine 1000 mg/m2, Vinorelbine 30 mg/m2 on day 1 and 8 intravenously with oral Prednisolone 100 mg/day on day 1 - 5) were given. Response evaluation done according to Cotswolds meeting recommendations and toxicity was evaluated with NCI-CTC (National Cancer Institute - Common Terminology Criteria for adverse events v 3.0). Results: Forty patients completing 4 cycles of GVP, 14 refractory/early relapse and 26 late relapsed (one year postprimary treatment with ABVD) were available for evaluation. The overall response (CRu+PR) rate was 77.5% with better response 85% in late relapsed patients. Haematological toxicity was most common and seen in 70% of cases. Conclusion: GVP is well-tolerated regimen with high response rate and needs to be tested in late relapsed HL. (author)

  4. Consolidation of long-term memory: Evidence and alternatives.

    OpenAIRE

    Meeter, M.; Murre, J.M.J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of amnesia, but they have not elucidated how consolidation must be envisaged. Here findings are reviewed that shed light on how consolidation may be impleme...

  5. Consolidation of the formation sand by chemical methods

    Directory of Open Access Journals (Sweden)

    Mariana Mihočová

    2006-10-01

    Full Text Available The sand control by consolidation involves the process of injecting chemicals into the naturally unconsolidated formation to provide an in situ grain-to-grain cementation. The sand consolidation chemicals are available for some 30 years. Several types of consolidating material were tried. Presently available systems utilize solidified plastics to provide the cementation. These systems include phenol resin, phenol-formaldehyde, epoxy, furan and phenolic-furfuryl.The sand consolidation with the steam injection is a novel technique. This process provides a highly alkaline liquid phase and temperatures to 300 °C to geochemically create cements by interacting with the dirty sand.While the formation consolidation has widely applied, our experience has proved a high level of success.

  6. Distributed learning enhances relational memory consolidation.

    Science.gov (United States)

    Litman, Leib; Davachi, Lila

    2008-09-01

    It has long been known that distributed learning (DL) provides a mnemonic advantage over massed learning (ML). However, the underlying mechanisms that drive this robust mnemonic effect remain largely unknown. In two experiments, we show that DL across a 24 hr interval does not enhance immediate memory performance but instead slows the rate of forgetting relative to ML. Furthermore, we demonstrate that this savings in forgetting is specific to relational, but not item, memory. In the context of extant theories and knowledge of memory consolidation, these results suggest that an important mechanism underlying the mnemonic benefit of DL is enhanced memory consolidation. We speculate that synaptic strengthening mechanisms supporting long-term memory consolidation may be differentially mediated by the spacing of memory reactivation. These findings have broad implications for the scientific study of episodic memory consolidation and, more generally, for educational curriculum development and policy.

  7. Dysfunctional overnight memory consolidation in ecstasy users.

    Science.gov (United States)

    Smithies, Vanessa; Broadbear, Jillian; Verdejo-Garcia, Antonio; Conduit, Russell

    2014-08-01

    Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naïve healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users. © The Author(s) 2014.

  8. 77 FR 17091 - Trust Land Consolidation Draft Plan

    Science.gov (United States)

    2012-03-23

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Trust Land Consolidation Draft Plan AGENCY... reopening the period for commenting on the Cobell Land Consolidation Program Draft Plan (also known as the Trust Land Consolidation Draft Plan), which is the draft plan for accomplishing these goals. DATES...

  9. Changing the countryside by land consolidation

    NARCIS (Netherlands)

    Benthem, Roelof Jan

    Land consolidation is a system of technical and legal measures for the improvement of farming conditions and land productivity. In western and central Europe, the execution of these land consolidation schemes causes great changes in the appearance of the countryside: existing landscape elements such

  10. Process for soil consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Herrick, F W; Brandstrom, R I

    1967-01-09

    In this process for the formation of a consolidated aggregate, a mass of solid particles is combined with an aqueous alkaline consolidating compound which forms a gel. This gel consists principally of a mixture of the following: a vegetable polyphenolic material; one of the group of catechins; condensed tannins and extract of the bark of coniferous trees; with 1-10% by weight of formaldehyde; and a catalyst of the group of water-soluble salts of chromium, iron, and aluminum. This catalyst serves to catalyze the reaction of formation of the gel.

  11. Apparatus for consolidation of earth formations

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, H

    1968-02-08

    Earth formations are consolidated by injecting into the formation a fluid medium through vertically spaced perforations; a device lowered into the borehole permits creating chambers isolated from each other and communicating with only one, or a group of perforations. These chambers are connected through valved conduits to a reservoir of the consolidating medium. Each chamber or each group of chambers has its own supply conduit, and flow-measuring means are provided in each conduit. The valves may be magnetic valves, controlled electrically from the surface; the reservoirs for the consolidating medium may be equipped with hydraulically actuated pistons. (8 claims)

  12. [The consolidation of memory, one century on].

    Science.gov (United States)

    Prado-Alcala, R A; Quirarte, G L

    The theory of memory consolidation, based on the work published by Georg Elias Muller and Alfons Pilzecker over a century ago, continues to guide research into the neurobiology of memory, either directly or indirectly. In their classic monographic work, they concluded that fixing memory requires the passage of time (consolidation) and that memory is vulnerable during this period of consolidation, as symptoms of amnesia appear when brain functioning is interfered with before the consolidation process is completed. Most of the experimental data concerning this phenomenon strongly support the theory. In this article we present a review of experiments that have made it possible to put forward a model that explains the amnesia produced in conventional learning conditions, as well as another model related to the protection of memory when the same instances of learning are submitted to a situation involving intensive training. Findings from relatively recent studies have shown that treatments that typically produce amnesia when they are administered immediately after a learning experience (during the period in which the memory would be consolidating itself) no longer have any effect when the instances of learning involve a relatively large number of trials or training sessions, or relatively high intensity aversive events. These results are not congruent with the prevailing theories about consolidation.

  13. 29 CFR 4011.6 - Mergers, consolidations, and spinoffs.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Mergers, consolidations, and spinoffs. 4011.6 Section 4011... REPORTING AND DISCLOSURE REQUIREMENTS DISCLOSURE TO PARTICIPANTS § 4011.6 Mergers, consolidations, and spinoffs. In the case of a plan involved in a merger, consolidation, or spinoff transaction that becomes...

  14. Synaptic consolidation across multiple timescales

    Directory of Open Access Journals (Sweden)

    Lorric Ziegler

    2014-03-01

    Full Text Available The brain is bombarded with a continuous stream of sensory events, but retains only a small subset in memory. The selectivity of memory formation prevents our memory from being overloaded with irrelevant items that would rapidly bring the brain to its storage limit; moreover, selectivity also prevents overwriting previously formed memories with new ones. Memory formation in the hippocampus, as well as in other brain regions, is thought to be linked to changes in the synaptic connections between neurons. In this view, sensory events imprint traces at the level of synapses that reflect potential memory items. The question of memory selectivity can therefore be reformulated as follows: what are the reasons and conditions that some synaptic traces fade away whereas others are consolidated and persist? Experimentally, changes in synaptic strength induced by 'Hebbian' protocols fade away over a few hours (early long-term potentiation or e-LTP, unless these changes are consolidated. The experiments and conceptual theory of synaptic tagging and capture (STC provide a mechanistic explanation for the processes involved in consolidation. This theory suggests that the initial trace of synaptic plasticity sets a tag at the synapse, which then serves as a marker for potential consolidation of the changes in synaptic efficacy. The actual consolidation processes, transforming e-LTP into late LTP (l-LTP, require the capture of plasticity-related proteins (PRP. We translate the above conceptual model into a compact computational model that accounts for a wealth of in vitro data including experiments on cross-tagging, tag-resetting and depotentiation. A central ingredient is that synaptic traces are described with several variables that evolve on different time scales. Consolidation requires the transmission of information from a 'fast' synaptic trace to a 'slow' one through a 'write' process, including the formation of tags and the production of PRP for the

  15. The nature of short-term consolidation in visual working memory.

    Science.gov (United States)

    Ricker, Timothy J; Hardman, Kyle O

    2017-11-01

    Short-term consolidation is the process by which stable working memory representations are created. This process is fundamental to cognition yet poorly understood. The present work examines short-term consolidation using a Bayesian hierarchical model of visual working memory recall to determine the underlying processes at work. Our results show that consolidation functions largely through changing the proportion of memory items successfully maintained until test. Although there was some evidence that consolidation affects representational precision, this change was modest and could not account for the bulk of the consolidation effect on memory performance. The time course of the consolidation function and selective influence of consolidation on specific serial positions strongly indicates that short-term consolidation induces an attentional blink. The blink leads to deficits in memory for the immediately following item when time pressure is introduced. Temporal distinctiveness accounts of the consolidation process are tested and ruled out. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase III of the Prototypical Rod Consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod Consolidation System as described in the NUS Phase II Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase III effort the system was tested on a component, subsystem, and system level. Volume IV provides the Operating and Maintenance Manual for the Prototypical Rod Consolidation System that was installed at the Cold Test Facility. This document, Book 1 of Volume IV, discusses: Process overview functional descriptions; Control system descriptions; Support system descriptions; Maintenance system descriptions; and Process equipment descriptions

  17. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase III of the Prototypical Rod Consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod Consolidation System as described in the NUS Phase II Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase III effort the system was tested on a component, subsystem, and system level. Volume IV provides the Operating and Maintenance Manual for the Prototypical Rod Consolidation System that was installed at the Cold Test Facility. This document, Book 4 of Volume IV, discusses: Off-normal operating and recovery procedures; Emergency response procedures; Troubleshooting procedures; and Preventive maintenance procedures

  18. Genesis and Development of Consolidated Financial Statements

    OpenAIRE

    Kostyantyn Bezverkhiy

    2015-01-01

    In the context of economy globalization it is the mission of consolidated financial statements to meet demands of users for financial information about activities of a company group as one company. The article is devoted to study of genesis and development of consolidated financial statements of companies. Historical prerequisites of genesis of consolidated financial statements are shown as well as factors which conduced to their spreading. The approaches are elucidated to preparation of cons...

  19. Control of Bank Consolidated Financial Statements Quality

    OpenAIRE

    Margarita S. Ambarchyan

    2013-01-01

    The author presents the multiple linear regression model of bank consolidated financial statements quality. The article considers six characteristics that can be used to estimate the level of bank consolidated financial statements quality. The multiple linear regression model was developed, using the results of point-based system of consolidated financial statements of thirty European bank and financial groups on the basis of the developed characteristics. The author offers to use the charact...

  20. 24 CFR 92.608 - Consolidated plan.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consolidated plan. 92.608 Section 92.608 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608 Consolidated...

  1. 10 CFR 1040.123 - Consolidated or joint hearings.

    Science.gov (United States)

    2010-01-01

    ... ACTIVITIES Enforcement Opportunity for Hearing § 1040.123 Consolidated or joint hearings. In cases in which... 10 Energy 4 2010-01-01 2010-01-01 false Consolidated or joint hearings. 1040.123 Section 1040.123... departments or agencies, where applicable, provide for the conduct of consolidated or joint hearings and for...

  2. Reward value determines memory consolidation in parasitic wasps.

    Science.gov (United States)

    Kruidhof, H Marjolein; Pashalidou, Foteini G; Fatouros, Nina E; Figueroa, Ilich A; Vet, Louise E M; Smid, Hans M; Huigens, Martinus E

    2012-01-01

    Animals can store learned information in their brains through a series of distinct memory forms. Short-lasting memory forms can be followed by longer-lasting, consolidated memory forms. However, the factors determining variation in memory consolidation encountered in nature have thus far not been fully elucidated. Here, we show that two parasitic wasp species belonging to different families, Cotesia glomerata (Hymenoptera: Braconidae) and Trichogramma evanescens (Hymenoptera; Trichogrammatidae), similarly adjust the memory form they consolidate to a fitness-determining reward: egg-laying into a host-insect that serves as food for their offspring. Protein synthesis-dependent long-term memory (LTM) was consolidated after single-trial conditioning with a high-value host. However, single-trial conditioning with a low-value host induced consolidation of a shorter-lasting memory form. For Cotesia glomerata, we subsequently identified this shorter-lasting memory form as anesthesia-resistant memory (ARM) because it was not sensitive to protein synthesis inhibitors or anesthesia. Associative conditioning using a single reward of different value thus induced a physiologically different mechanism of memory formation in this species. We conclude that the memory form that is consolidated does not only change in response to relatively large differences in conditioning, such as the number and type of conditioning trials, but is also sensitive to more subtle differences, such as reward value. Reward-dependent consolidation of exclusive ARM or LTM provides excellent opportunities for within-species comparison of mechanisms underlying memory consolidation.

  3. Consolidation treatments applied to ceramic tiles: are they homogeneous?

    International Nuclear Information System (INIS)

    Costa, D.; Leal, A.S.; Mimoso, J.M; Pereira, S.M.R.

    2017-01-01

    The mass consolidation treatment of azulejos is necessary when ceramic biscuits show signs of disaggregation. Such treatment is often used as a complementary conservation technique to the reestablishment of weakened glaze-ceramic bonds. In this research, two commonly used consolidants (ethyl silicate and acrylic resin) were tested on artisanal ceramic tiles via mass consolidation and the resulting impregnation profiles were evaluated. The results indicated that after consolidation, hard zones frequently formed due to localized consolidant concentration after the polymerization and curing processes. These inhomogeneous hard zones subsequently influenced the results obtained through conventional mechanical strength testing (i.e. flexural and compression), creating a false impression of success. This research demonstrated that by using the Drilling Resistance Measuring System, impregnation characteristics such as penetration depth and distribution of consolidant could be observed that otherwise could not be discerned through the more common testing methods. As such, a more extensive evaluation of consolidation effects was achieved. [es

  4. Consolidation treatments applied to ceramic tiles: are they homogeneous?

    Directory of Open Access Journals (Sweden)

    D. Costa

    2017-01-01

    Full Text Available The mass consolidation treatment of azulejos is necessary when ceramic biscuits show signs of disaggregation. Such treatment is often used as a complementary conservation technique to the reestablishment of weakened glaze-ceramic bonds. In this research, two commonly used consolidants (ethyl silicate and acrylic resin were tested on artisanal ceramic tiles via mass consolidation and the resulting impregnation profiles were evaluated. The results indicated that after consolidation, hard zones frequently formed due to localized consolidant concentration after the polymerization and curing processes. These inhomogeneous hard zones subsequently influenced the results obtained through conventional mechanical strength testing (i.e. flexural and compression, creating a false impression of success. This research demonstrated that by using the Drilling Resistance Measuring System, impregnation characteristics such as penetration depth and distribution of consolidant could be observed that otherwise could not be discerned through the more common testing methods. As such, a more extensive evaluation of consolidation effects was achieved.

  5. CONSOLIDATED FINANCIAL STATEMENTS UNDER IFRS

    OpenAIRE

    Tănase Alin-Eliodor; Calotă Traian-Ovidiu

    2013-01-01

    This article is focuses on accounting consolidation techniques and the preparation of consolidation worksheets for the components of financial statements (statement of comprehensive income, statement of changes in equity, and financial position). The presented group includes parent company, two subsidiaries (only one fully controlled by the parent company) and a jointly controlled entity. The financial statements are presented under the following standards IFRS 3 Business Combination, IAS 27 ...

  6. 10 CFR 4.64 - Consolidated or joint hearings.

    Science.gov (United States)

    2010-01-01

    ... Consolidated or joint hearings. In cases in which the same or related facts are asserted to constitute... 10 Energy 1 2010-01-01 2010-01-01 false Consolidated or joint hearings. 4.64 Section 4.64 Energy... or agencies, where applicable, provide for the conduct of consolidated or joint hearings, and for the...

  7. Consolidated Lunar Atlas

    Data.gov (United States)

    National Aeronautics and Space Administration — The Consolidated Lunar Atlas is a collection of the best photographic images of the moon, including low-oblique photography, full-moon photography, and tabular and...

  8. 26 CFR 1.1502-21A - Consolidated net operating loss deduction generally applicable for consolidated return years...

    Science.gov (United States)

    2010-04-01

    ... operating loss attributable to such member. (iii) Foreign expropriation losses. An election under section... expropriation loss) may be made for a consolidated return year only if the sum of the foreign expropriation... expropriation losses, or (b) the consolidated net operating loss. (3) Absorption rules. For purposes of...

  9. Sandia solidification process: consolidation and characterization. Part I. Consolidation studies

    International Nuclear Information System (INIS)

    Johnstone, J.K.

    1978-05-01

    The consolidation behavior of a complex polycrystalline ceramic nuclear waste form composed of titanates, zeolite, and metallic silicon was studied. Initial solidification takes place by an ion exchange process. The resulting powder exhibits a large surface area, approximately 350 m 2 /g, and several decomposition, crystallization and phase change reactions from room temperature to 1100 0 C. In spite of the large surface area, consolidation by cold pressing and atmospheric sintering to 1100 0 C was not satisfactory. Vacuum hot pressing was found to produce fully dense pellets (less than 1% residual porosity) under very mild conditions, 6.9 MPa (1100 psi) and 1100 0 C. The dominant densification mechanism was viscous flow. Under less than optimum hot pressing conditions, three stages of densification were observed. Initial densification took place by particle rearrangement which was described with a viscous flow model. Second stage densification occurred by a solution-precipitation process controlled by a phase boundary dissolution reaction. In several cases, a third, final densification stage was observed. Detailed studies describe the effects of heating rate, processing temperature, pressure, residence time, atmosphere, composition, heat treatment, and the addition of consolidation aids on the densification behavior. In addition, fully radioactive high level mixed fission product titanate/waste pellets (1.27 cm diameter) were hot pressed at Oak Ridge National Laboratory to demonstrate the feasibility of such a process in a remotely operated hot cell. High density uniform pellets were obtained

  10. The consolidation of annual accounts in the Swiss Federal Government

    OpenAIRE

    Vollenweider, Petra

    2011-01-01

    Financial reporting in the public sector is influenced by the private sector accounting standards. The Swiss Federal Government has recently started to prepare consolidated financial statements. The purpose of this study is to describe how the Swiss Federal Government is doing its consolidated financial statements. Theoretically there are different consolidation theories and methods. The choice of consolidation method can explain which consolidation theory is used when the financial statement...

  11. Operation and consolidation: lifetime of equipment and priorities TS

    CERN Document Server

    Béjar-Alonso, Isabel

    2008-01-01

    Since 1999 the TS department has benchmarked his services with the industry and other research laboratories and has prepared several consolidation plans. An evaluation of the results obtained from the different consolidation plans will be summarized. The difference between the projects achieved and those planned will be analyzed. The impact of the differed consolidation and of the maintenance backlog will be analyzed in order to present the future TS consolidation strategy

  12. The insulin-like growth factor axis and collagen turnover during prednisolone treatment

    DEFF Research Database (Denmark)

    Wolthers, O D; Juul, A; Hansen, M

    1994-01-01

    Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and the aminoterminal propeptide...... of type III procollagen (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0 years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a randomised double blind crossover trial with run in, treatment, and washout periods of two weeks. No statistically significant...... effects on serum concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP, ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3) and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms...

  13. 20 CFR 410.646 - Consolidated issues.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Consolidated issues. 410.646 Section 410.646..., Finality of Decisions, and Representation of Parties § 410.646 Consolidated issues. When one or more additional issues are raised by the Administrative Law Judge pursuant to § 410.637, such issues may, in the...

  14. APPLICABILITY OF CONSOLIDATED TECHNIQUES IN THE VIEW OF ROMANIAN ACCOUNTING REGULATIONS

    Directory of Open Access Journals (Sweden)

    Cristina Rosu

    2016-06-01

    Full Text Available The accounting regulations are more and more interested in groups of companies. In some cases, these regulations require for preparing the consolidated financial statements. This is the task of the parent company who keeps the consolidated accounts. To accomplish its goals, the consolidated accounting uses a couple of, so-called, consolidation techniques. These are applied in the case of groups of companies with a complex structure. Their goal is to elaborate the consolidated financial statements using a set of methods and empirical skills. In this article we synthetize and apply the consolidation techniques in the view of Romanian accounting regulations. The Romanian practice has revealed, especially, two techniques: one based on direct consolidation and another one based on multiple levels (phased consolidation. Therefore, this work regards only the technical side of consolidated accounting, accounting records being evaded. Furthermore, we focus only on the preparation of the consolidated balance sheet in the case of some hypothetical groups of companies.

  15. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  16. Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

    Science.gov (United States)

    Barea, Silvana A; Mattos, Cristiane B; Cruz, Ariadne C C; Chaves, Vitor C; Pereira, Rafael N; Simões, Claudia M O; Kratz, Jadel M; Koester, Letícia S

    2017-03-01

    Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire ® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor ® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

  17. Large Strain Analysis of Electro-Osmosis Consolidation for Clays

    NARCIS (Netherlands)

    Yuan, J.

    2015-01-01

    Consolidation of soft clay creates a lot of problems in foundation engineering, because of the very low clay permeability and high compressibility. Primary consolidation takes a long time to complete if the material is left consolidating under atmospheric evaporation, and traditional dewatering

  18. An improved electrokinetic method to consolidate porous materials

    DEFF Research Database (Denmark)

    Feijoo, Jorge; Ottosen, Lisbeth M.; Nóvoa, X. R.

    2017-01-01

    the consolidation using commercial products have some limitations, such as: (1) low penetrability; (2) no chemical and mineralogical affinity with the material to treat and (3) release of toxic compounds (VOCs), during the solvent evaporation. In the last years, a new consolidation method based on electrokinetic...... the pH of the solutions in contact with the porous material, which can damage it and (2) it is difficult to determine in which area the consolidation takes place. In this study an electrokinetic consolidation method, which has two steps between which the current is reversed, is proposed to solve all...... techniques was developed. This method allows filling some pores by the precipitation of an inorganic compound. As a result the method allows increasing the penetration depth of current consolidation treatments. However, this method needs to be improved since: (1) no special care is taking in controlling...

  19. Sleep-related memory consolidation in primary insomnia.

    Science.gov (United States)

    Nissen, Christoph; Kloepfer, Corinna; Feige, Bernd; Piosczyk, Hannah; Spiegelhalder, Kai; Voderholzer, Ulrich; Riemann, Dieter

    2011-03-01

    It has been suggested that healthy sleep facilitates the consolidation of newly acquired memories and underlying brain plasticity. The authors tested the hypothesis that patients with primary insomnia (PI) would show deficits in sleep-related memory consolidation compared to good sleeper controls (GSC). The study used a four-group parallel design (n=86) to investigate the effects of 12 h of night-time, including polysomnographically monitored sleep ('sleep condition' in PI and GSC), versus 12 h of daytime wakefulness ('wake condition' in PI and GSC) on procedural (mirror tracing task) and declarative memory consolidation (visual and verbal learning task). Demographic characteristics and memory encoding did not differ between the groups at baseline. Polysomnography revealed a significantly disturbed sleep profile in PI compared to GSC in the sleep condition. Night-time periods including sleep in GSC were associated with (i) a significantly enhanced procedural and declarative verbal memory consolidation compared to equal periods of daytime wakefulness in GSC and (ii) a significantly enhanced procedural memory consolidation compared to equal periods of daytime wakefulness and night-time sleep in PI. Across retention intervals of daytime wakefulness, no differences between the experimental groups were observed. This pattern of results suggests that healthy sleep fosters the consolidation of new memories, and that this process is impaired for procedural memories in patients with PI. Future work is needed to investigate the impact of treatment on improving sleep and memory. © 2010 European Sleep Research Society.

  20. Status of rod consolidation

    International Nuclear Information System (INIS)

    Bailey, W.J.

    1985-04-01

    Two of the factors that need to be taken into account with rod consolidation are (1) the effects on rods from their removal from the fuel assembly and (2) the effects on rods as a result of the consolidation process. Potential components of both factors are described in the report. Discussed under (1) are scratches on the fuel rod surfaces, rod breakage, crud, extended burnup, and possible cladding embrittlement due to hydrogen injection at BWRs. Discussed under (2) are the increased water temperature (less than 10 0 C) because of closer packing of the rods, formation of crevices between rods in the close-packed mode, contact with dissimilar metals, and the potential for rapid heating of fuel rods following the loss of water from a spent fuel storage pool. Another factor that plays an important role in rod consolidation is the cost of disposal of the nonfuel-bearing components of the fuel assembly. Also, the dose rate from the components - especially Inconel spacer grids - can affect the handling procedures. Several licensing issues that exist are described. A list of recommendations is provided. 98 refs., 5 figs., 5 tabs

  1. Delayed working memory consolidation during the attentional blink.

    Science.gov (United States)

    Vogel, Edward K; Luck, Steven J

    2002-12-01

    After the detection of a target (T1) in a rapid stream of visual stimuli, there is a period of 400-600 msec during which a subsequent target (T2) is missed. This impairment in performance has been labeled the attentional blink. Recent theories propose that the attentional blink reflects a bottleneck in working memory consolidation such that T2 cannot be consolidated until after T1 is consolidated, and T2 is therefore masked by subsequent stimuli if it is presented while T1 is being consolidated. In support of this explanation, Giesbrecht & Di Lollo (1998) found that when T2 is the final item in the stimulus stream, no attentional blink is observed, because there are no subsequent stimuli that might mask T2. To provide a direct test of this explanation of the attentional blink, in the present study we used the P3 component of the event-related potential waveform to track the processing of T2. When T2 was followed by a masking item, we found that the P3 wave was completely suppressed during the attentional blink period, indicating that T2 was not consolidated in working memory. When T2 was the last item in the stimulus stream, however, we found that the P3 wave was delayed but not suppressed, indicating that T2 consolidation was not eliminated but simply delayed. These results are consistent with a fundamental limit on the consolidation of information in working memory.

  2. Cost targets for at-reactor spent fuel rod consolidation

    International Nuclear Information System (INIS)

    Macnabb, W.V.

    1985-01-01

    The high-level nuclear waste management system in the US currently envisions the disposal of spent fuel rods that have been removed from their assemblies and reconfigured into closely packed arrays. The process of fuel rod removal and packaging, referred to as rod consolidation, can occur either at reactors or at an integrated packaging facility, monitored retrievable storage (MRS). Rod consolidation at reactors results in cost savings down stream of reactors by reducing needs for additional storage, reducing the number of shipments, and reducing (eliminating, in the extreme) the amount of fuel handling and consolidation at the MRS. These savings accrue to the nuclear waste fund. Although private industry is expected to pay for at-reactor activities, including rod consolidation, it is of interest to estimate cost savings to the waste system if all fuel were consolidated at reactors. If there are savings, the US Department of Energy (DOE) may find it advantageous to pay for at-reactor rod consolidation from the nuclear waste fund. This paper assesses and compares the costs of rod consolidation at reactors and at the MRS in order to determine at what levels the former could be cost competitive with the latter

  3. Implementation of a consolidated, standardized database of environmental measurements data

    International Nuclear Information System (INIS)

    James, T.L.

    1996-10-01

    This report discusses the benefits of a consolidated and standardized database; reasons for resistance to the consolidation of data; implementing a consolidated database, including attempts at standardization, deciding what to include in the consolidated database, establishing lists of valid values, and addressing quality assurance/quality control (QA/QC) issues; and the evolution of a consolidated database, which includes developing and training a user community, resolving configuration control issues, incorporating historical data, identifying emerging standards, and developing pointers to other data. OREIS is used to illustrate these topics

  4. Addition of a Short Course of Prednisolone to a Gluten-Free Diet vs. Gluten-Free Diet Alone in Recovery of Celiac Disease: A Pilot Randomized Controlled Trial.

    Science.gov (United States)

    Abbas, Asad; Shahab, Tabassum; Sherwani, Rana K; Alam, Seema

    2018-01-28

    Background A gluten-free diet (GFD) is the standard of care in the management of patients with celiac disease, but clinical and histological recovery are often delayed. In newly diagnosed patients, strict compliance to GFD is difficult to achieve; this is especially true in developing countries where gluten-free food is often difficult to obtain. Steroids, when used alone, can be effective in inducing recovery in patients with celiac disease. We performed a randomized controlled trial to study the effect of a short course of prednisolone combined with a GFD on the recovery of celiac disease. Materials and methods This study was a single-center, randomised, open-label trial. This investigation was done in a pediatric gastroenterology unit of a tertiary teaching hospital in north India.Twenty-eight newly diagnosed celiac disease patients were enrolled in the study. Prednisolone was given at 1 mg/kg for four weeks; duodenal biopsies and IgA anti-tissue transglutaminase (tTg) levels were assessed at eight weeks, six months, and 12 months from the start of the study. Outcome measures The primary outcome measures used to indicate clinical, histological, and immunological recovery of celiac disease were clinical improvement at eight weeks and the proportion of patients with improved histology by at least one grade and who were tissue transglutaminase (tTg) seronegative at eight weeks. The secondary measures were the proportion of patients showing normalization of histological features and the proportions of patients becoming seronegative at six months and one year of GFD. Results Patients were randomized into the GFD only (n = 14) or GFD with prednisolone (GFD+P) (n = 14) groups. No significant differences were detected in clinical recovery at eight weeks; none of the patients became seronegative at eight weeks, six months, or 12 months. The proportion of patients with improvement in histology by at least one grade was higher in the GFD+P group at eight weeks, and there

  5. Usage of internal statements in making consolidated financial statement

    Directory of Open Access Journals (Sweden)

    V.N. Herman

    2016-12-01

    Full Text Available The emergence of the consolidated financial statements is the result of integration processes in the businesses that lead to pooling of different companies. As consolidated financial statements present an aggregated look at the financial position of a parent and its subsidiaries, they let you gauge the overall health of an entire group of companies as opposed to one company’s standalone position. Consolidation of financial statements requires from the participants of joining elaborating their individual statements. The article describes the general scheme of consolidation process and defines the key trends of consolidation adjustments, in particular, financial investments, internal operations, goodwill and exchange rate differences. It is found out that to get information about internal operations and financial investments such data have to be synthesized from internal statements. This approach allows using the same accounting methods to parent and subsidiary entities. The objects, the users and the subject domain of internal statements are determined in order to make consolidation of financial statements of joining.

  6. Tomographic findings of lobar consolidation in primary pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Pereira, Bruno Alberto Falcao; Macedo, Solange Goncalves David de; Penna, Claudia Renata Rezende

    2009-01-01

    Objective: To describe tomographic findings of lobar consolidation as early manifestation of primary pulmonary tuberculosis. Materials and methods: The present study was developed at Hospital Municipal Jesus, Rio de Janeiro, RJ, Brazil, in the period between 2002 and 2006, retrospectively evaluating tomographic findings in four children aged from 3 to 14 months with lobar consolidation as an early manifestation of primary pulmonary tuberculosis. Results: The most frequently found radiological pattern was lobar consolidation with calcifications, cavitation and intermingle necrotic areas, associated with bulging fissure. Signs of bronchogenic dissemination and lymph node enlargement were observed in all of the four children. Consolidation with a pseudotumor aspect and masslike effect was observed in one case. Conclusion: The cases included in the present study have demonstrated that primary pulmonary tuberculosis manifested as lobar consolidation presents typical tomographic images such as cavitation, hypodense areas and calcifications intermingled with consolidation. The association with lymph node enlargement with central necrosis and signs of bronchogenic dissemination reinforce the diagnosis of tuberculosis. (author)

  7. Creep consolidation of nuclear depository backfill materials

    International Nuclear Information System (INIS)

    Butcher, B.M.

    1980-10-01

    Evaluation of the effects of backfilling nuclear waste repository rooms is an important aspect of waste repository design. Consolidation of the porous backfill takes place as the room closes with time, causing the supporting stress exerted by the backfill against the intact rock to increase. Estimation of the rate of backfill consolidation is required for closure rate predictions and should be possible if the creep law for the solid constituent is known. A simple theory describing consolidation with a spherical void model is derived to illustrate this relationship. Although the present form of the theory assumes a homogeneous isotropic incompressible material atypical of most rocks, it may be applicable to rock salt, which exhibits considerable plasticity under confined pressure. Application of the theory is illustrated assuming a simple steady-state creep law, to show that the consolidation rate depends on the externally applied stress, temperature, and porosity

  8. Memory processes during sleep: beyond the standard consolidation theory.

    Science.gov (United States)

    Axmacher, Nikolai; Draguhn, Andreas; Elger, Christian E; Fell, Juergen

    2009-07-01

    Two-step theories of memory formation suggest that an initial encoding stage, during which transient neural assemblies are formed in the hippocampus, is followed by a second step called consolidation, which involves re-processing of activity patterns and is associated with an increasing involvement of the neocortex. Several studies in human subjects as well as in animals suggest that memory consolidation occurs predominantly during sleep (standard consolidation model). Alternatively, it has been suggested that consolidation may occur during waking state as well and that the role of sleep is rather to restore encoding capabilities of synaptic connections (synaptic downscaling theory). Here, we review the experimental evidence favoring and challenging these two views and suggest an integrative model of memory consolidation.

  9. 26 CFR 1.1502-4 - Consolidated foreign tax credit.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated foreign tax credit. 1.1502-4... TAX (CONTINUED) INCOME TAXES Consolidated Tax Liability § 1.1502-4 Consolidated foreign tax credit. (a) In general. The credit under section 901 for taxes paid or accrued to any foreign country or...

  10. Factors affecting the consolidation of steam generator sludge

    Energy Technology Data Exchange (ETDEWEB)

    Turner, C. W.; Shamsuzzaman, K.; Tapping, R. L.

    1993-02-15

    It is hypothesized that sludge consolidation is promoted by chemical reactions involving the various sludge constituents, although the hardness of the final product will also depend on the total porosity. Oxidizing conditions and higher temperatures produce a harder sludge. The precipitation of Zn{sub 2}SiO{sub 4}, a potential binding agent, may also promote sludge consolidation. Several solutions to prevent sludge consolidation are suggested. (Author) 3 figs., 4 tabs., 3 refs.

  11. Sleep enhances memory consolidation in children.

    Science.gov (United States)

    Ashworth, Anna; Hill, Catherine M; Karmiloff-Smith, Annette; Dimitriou, Dagmara

    2014-06-01

    Sleep is an active state that plays an important role in the consolidation of memory. It has been found to enhance explicit memories in both adults and children. However, in contrast to adults, children do not always show a sleep-related improvement in implicit learning. The majority of research on sleep-dependent memory consolidation focuses on adults; hence, the current study examined sleep-related effects on two tasks in children. Thirty-three typically developing children aged 6-12 years took part in the study. Actigraphy was used to monitor sleep. Sleep-dependent memory consolidation was assessed using a novel non-word learning task and the Tower of Hanoi cognitive puzzle, which involves discovering an underlying rule to aid completion. Children were trained on the two tasks and retested following approximately equal retention intervals of both wake and sleep. After sleep, children showed significant improvements in performance of 14% on the non-word learning task and 25% on the Tower of Hanoi task, but no significant change in score following the wake retention interval. Improved performance on the Tower of Hanoi may have been due to children consolidating explicit aspects of the task, for example rule-learning or memory of previous sequences; thus, we propose that sleep is necessary for consolidation of explicit memory in children. Sleep quality and duration were not related to children's task performance. If such experimental sleep-related learning enhancement is generalizable to everyday life, then it is clear that sleep plays a vital role in children's educational attainment. © 2013 European Sleep Research Society.

  12. Agentes imunossupressores, talidomida e ácido valpróico nas síndromes mielodisplásicas Immunosuppressive agents, thalidomide and valproate acid in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elvira R. P. Velloso

    2006-09-01

    Full Text Available Agentes imunossupressores, como a globulina antitimocítica (GAL ou antilinfocítica (GAL e a ciclosporina A têm mostrado eficácia nas SMD, particularmente nos subtipos Anemias refratária (AR e nas SMD com fenótipo HLA-DR15, independente do grau de celularidade medular. Outras drogas disponíveis em nosso meio, de baixo custo, como a talidomida podem ser utilizada em pacientes refratários, e o ácido valpróico está sendo utilizado em ensaios clínicos. A quantificação da resposta a drogas deve utilizar os critérios de resposta do International Working Group (IWG. É proposto um fluxograma para uso de fatores de crescimento, agentes imunossupressores e talidomida em pacientes com SMD, de baixo risco, não candidatos a transplante de medula óssea (TMO.Patients with refractory anemia subtypes and HLA-DR15 with any degree of marrow cellularity have good responses to immunosuppressive agents, such as antithymocyte globulin, antilymphocyte globulin and cyclosporine A. Other cheaper drugs available in Brazil, including thalidomide may be useful in refractory patients. Valproate acid has started to be used in clinical trials. Response to treatment should be reported using the criteria proposed by the International Working Group. The use of growth factors, immunosuppressive agents and thalidomide in low risk patients with myelodysplastic syndromes who are not candidates for hematopoietic stem cell transplantation is suggested at the end of this publication.

  13. The new wave of hospital consolidation.

    Science.gov (United States)

    Goldstein, Lisa

    2012-04-01

    Reimbursement challenges, spiraling healthcare costs, and a slow economic recovery are driving the latest wave of hospital consolidation. Health insurance companies and provider systems are forming partnerships in the consolidation field with the goal of reducing healthcare costs and improving quality. The "cost" of the acquisition may include debt and other obligations of the acquired hospital, such as pension liabilities, along with a multiyear capital commitment.

  14. Theoretical Consolidation of Acoustic Dissipation

    Science.gov (United States)

    Casiano, M. J.; Zoladz, T. F.

    2012-01-01

    In many engineering problems, the effects of dissipation can be extremely important. Dissipation can be represented by several parameters depending on the context and the models that are used. Some examples of dissipation-related parameters are damping ratio, viscosity, resistance, absorption coefficients, pressure drop, or damping rate. This Technical Memorandum (TM) describes the theoretical consolidation of the classic absorption coefficients with several other dissipation parameters including linearized resistance. The primary goal of this TM is to theoretically consolidate the linearized resistance with the absorption coefficient. As a secondary goal, other dissipation relationships are presented.

  15. 7 CFR 1782.15 - Mergers and consolidations.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Mergers and consolidations. 1782.15 Section 1782.15... AGRICULTURE (CONTINUED) SERVICING OF WATER AND WASTE PROGRAMS § 1782.15 Mergers and consolidations. Mergers... transaction under consideration and the unique facts involved in each transaction. Mergers occur when two or...

  16. 'Consolidation' of HVAC and cooling systems at CERN

    CERN Document Server

    Inigo-Golfin, J; Pepinster, P; CERN. Geneva. TS Department

    2008-01-01

    A â€ワconsolidation” of installations after they have reached the end of their predetermined life-time is part of the life cycle of industrial installations, regardless how well maintained they are. The â€ワconsolidation” plan might cover the replacement of obsolete equipment, partial refurbishment, the work requested to comply with new standards and applicable rules (environmental aspects) until the complete replacement of the whole installation. This â€ワconsolidation” process is all the more critical since the installation dates of the existing cooling and HVAC equipment at CERN spans over a period of 50 years and â€ワconsolidation” in the past has been not been systematic, being most of the time associated with new projects. This paper describes the reasons behind the recent â€ワconsolidation” requests for cooling and HVAC equipment both for the accelerators backbone and in tertiary buildings. A criticality analysis is given, based on the criteria laid down in the p...

  17. Similarities and disparities between Romanian individual and consolidated financial group statements

    Directory of Open Access Journals (Sweden)

    Florentin Tanasa

    2012-12-01

    Full Text Available The purpose of this study is to identify, analyse and assess the main connections and implications of consolidated accounts on enterprise economy. Appearance of consolidated financial statements is intrinsically linked to certain concepts, such as group, control, the perimeter of consolidation, percentages of interests, methods of consolidation, or restatements. For a more complete view regarding consolidated annual accounts, it is necessary to delimit and define these particular elements. This approach targets the presentation of our vision over positioning, place and function of financial consolidated statements in the process of the financial report. The study envisages a summary and comparison of ideas found on this subject in thespecialty literature, the regulations developed by various international bodies. Thus, we think it will facilitate the correct positioning of the consolidated financial statements and the consolidated accounts’ concepts. To achieve the proposed desiderates, we have used a constructive methodology for identifying disagreements, approvals and development of a speech to more efficient and effective management of the mentioned concepts.

  18. 7 CFR 15.86 - Consolidated or joint hearings.

    Science.gov (United States)

    2010-01-01

    ... responsibility within the Department for the administration of all the laws extending the Federal financial... agreement order consolidation for hearing. The Secretary may order proceedings in the Department... such consolidation. Hearing Officer ...

  19. Consolidation and permeability of salt in brine

    International Nuclear Information System (INIS)

    Shor, A.J.; Baes, C.F. Jr.; Canonico, C.M.

    1981-07-01

    The consolidation and loss of permeability of salt crystal aggregates, important in assessing the effects of water in salt repositories, has been studied as a function of several variables. The kinetic behavior was similar to that often observed in sintering and suggested the following expression for the time dependence of the void fraction: phi(t) = phi(0) - (A/B)ln(1 + Bt/z(0) 3 ), where A and B are rate constants and z(0) is initial average particle size. With brine present, A and phi(0) varied linearly with stress. The initial void fraction was also dependent to some extent on the particle size distribution. The rate of consolidation was most rapid in brine and least rapid in the presence of only air as the fluid. A brine containing 5 m MgCl 2 showed an intermediate rate, presumably because of the greatly reduced solubility of NaCl. A substantial wall effect was indicated by an observed increase in the void fraction of consolidated columns with distance from the top where the stress was applied and by a dependence of consolidation rate on the column height and radius. The distance through which the stress fell by a factor of phi was estimated to change inversely as the fourth power of the column diameter. With increasing temperature (to 85 0 C), consolidation proceeded somewhat more rapidly and the wall effect was reduced. The permeability of the columns dropped rapidly with consolidation, decreasing with about the sixth power of the void fraction. In general, extrapolation of the results to repository conditions confirms the self-sealing properties of bedded salt as a storage medium for radioactive waste

  20. The neurobiology of consolidations, or, how stable is the engram?

    Science.gov (United States)

    Dudai, Yadin

    2004-01-01

    Consolidation is the progressive postacquisition stabilization of long-term memory. The term is commonly used to refer to two types of processes: synaptic consolidation, which is accomplished within the first minutes to hours after learning and occurs in all memory systems studied so far; and system consolidation, which takes much longer, and in which memories that are initially dependent upon the hippocampus undergo reorganization and may become hippocampal-independent. The textbook account of consolidation is that for any item in memory, consolidation starts and ends just once. Recently, a heated debate has been revitalized on whether this is indeed the case, or, alternatively, whether memories become labile and must undergo some form of renewed consolidation every time they are activated. This debate focuses attention on fundamental issues concerning the nature of the memory trace, its maturation, persistence, retrievability, and modifiability.

  1. Evaluation consolidated under Financial Group Banca Transilvania

    Directory of Open Access Journals (Sweden)

    Chebac Neculina

    2009-06-01

    Full Text Available One of the components of prudence measures adopted by the competentauthorities with the regulation and supervision of financial markets at national andEuropean level is mandatory consolidation of accounts. Romania as member of theEuropean Union it harmonized national regulations with the European consolidation ofaccounts of companies. For the banks have been issued by the appropriate rules by theregulators authority, concerned by National Bank of Romania. In accordance withnational regulations, companies are required to prepare annual consolidated financialstatements may make such situations according to the regulations or accounting inaccordance with Directive VII of the European Economic Community, underInternational Financial Reporting Standards.

  2. Physical and chemical factors affecting sludge consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Turner, C.W.; Blimkie, M.E.; Lavoie, P.A

    1997-09-01

    Chemical reactions between sludge components and precipitation reactions within the pores of the existing sludge are shown to contribute to the consolidation of sludge under steam generator operating conditions. Simulations of sludge representative of plants with a mixed iron/copper feedtrain suggest that as the conditions in the feedtrain become more oxidizing the sludge will become harder with a higher nickel ferrite content. The precipitation of feedwater impurities introduced by condenser leaks and of zinc silicate, which is produced in plants with brass condenser tubes and silica in the makeup water, contribute significantly to sludge consolidation. Sodium phosphate is also shown to be an agent of sludge consolidation. (author)

  3. Consolidating Financial Statements.

    Science.gov (United States)

    Wood, Marcia R.

    This publication is designed to be a desktop reference and assist financial officers in both public and independent institutions of higher education in the preparation of consolidated financial statements. Chapter 1 covers generally accepted accounting principles and other accounting literature, and summarizes reporting rules of the Financial…

  4. 7 CFR 1717.615 - Consolidations and mergers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Consolidations and mergers. 1717.615 Section 1717.615... Controls § 1717.615 Consolidations and mergers. A distribution or power supply borrower may without the..., merger, conveyance or transfer shall be on such terms as shall fully preserve the lien and security of...

  5. INEL integrated spent nuclear fuel consolidation task team report

    International Nuclear Information System (INIS)

    Henry, R.N.; Clark, J.H.; Chipman, N.A.

    1994-01-01

    This document describes a draft plan and schedule to consolidate spent nuclear fuel (SNF) and special nuclear material (SNW) from aging storage facilities throughout the Idaho National Engineering Laboratory (INEL) to the Idaho Chemical Processing Plant (ICPP) in a safe, cost-effective, and expedient manner. A fully integrated and resource-loaded schedule was developed to achieve consolidation as soon as possible. All of the INEL SNF and SNM management task, projects, and related activities from fiscal year 1994 to the end of the consolidation period are logic-tied and integrated with each other. The schedule and plan are presented to initiate discussion of their implementation, which is expected to generate alternate concepts that can be evaluated using the methodology described in this report. Three perturbations to consolidating SNF as soon as possible are also explored. If the schedule is executed as proposed, the new and on-going consolidation activities will require about 6 years to complete and about $25.3M of additional funding. Reduced annual operating costs are expected to recover the additional investment in about 6.4 years. The total consolidation program as proposed will cost about $66.8M and require about 6 years to recover via reduced operating costs from retired SNF/SNM storage facilities. Detailed schedules and cost estimates for the Test Reactor Area Materials Test Reactor canal transfers are included as an example of the level of detail that is typical of the entire schedule (see Appendix D). The remaining work packages for each of the INEL SNF consolidation transfers are summarized in this document. Detailed cost and resource information is available upon request for any of the SNF consolidation transfers

  6. [Evaluation of ecosystem service value and strategies for ecological design in land consolidation: a case of land consolidation project in Da'an City, Jilin Province, China].

    Science.gov (United States)

    Wang, Jun; Yan, Shen-Chun; Yu, Li; Zhang, Ya-Nan

    2014-04-01

    Land consolidation, as one of the major driving forces for the changes of land use/cover, has significant impacts on landscape patterns, ecological functions, and ecosystem services. In this paper, a land consolidation project conducted in Da'an City, Jinlin Province, China, was selected to evaluate the ecosystem service values before and after land consolidation at three spatial scales, i. e., village, town, and county. The results indicated that the land consolidation with the goal to increase the area of cultivated land might cause the decrease of the saline and alkaline land, grassland, and wetland. In addition, land consolidation resulted in the reduction of the total ecosystem service values at varying degree at the three scales. Compared to the pre-consolidation status, the total post-consolidation ecosystem service values at the village, town and county scales were 7.96, 843.01 and 1205.86 million yuan, and reduced by 10.5%, 14.2% and 33.1%, respectively. Based on the evaluation of ecosystem service value, strategies of landscape ecological design were discussed to improve the ecological functions and to provide the guidance for the sustainable development of land consolidation.

  7. The Behavior and Durability of Self-Consolidating Concrete.

    Science.gov (United States)

    2015-05-01

    This report focuses on the production of self-consolidating concrete using local materials from Las Vegas, Nevada. Tests were conducted on eight self-consolidating concrete mixtures having two different percentages of fly-ash replacement (25% and 35%...

  8. 100-N pilot project: Proposed consolidated groundwater monitoring program

    International Nuclear Information System (INIS)

    Borghese, J.V.; Hartman, M.J.; Lutrell, S.P.; Perkins, C.J.; Zoric, J.P.; Tindall, S.C.

    1996-11-01

    This report presents a proposed consolidated groundwater monitoring program for the 100-N Pilot Project. This program is the result of a cooperative effort between the Hanford Site contractors who monitor the groundwater beneath the 100-N Area. The consolidation of the groundwater monitoring programs is being proposed to minimize the cost, time, and effort necessary for groundwater monitoring in the 100-N Area, and to coordinate regulatory compliance activities. The integrity of the subprograms requirements remained intact during the consolidation effort. The purpose of this report is to present the proposed consolidated groundwater monitoring program and to summarize the process by which it was determined

  9. Dreaming and offline memory consolidation.

    Science.gov (United States)

    Wamsley, Erin J

    2014-03-01

    Converging evidence suggests that dreaming is influenced by the consolidation of memory during sleep. Following encoding, recently formed memory traces are gradually stabilized and reorganized into a more permanent form of long-term storage. Sleep provides an optimal neurophysiological state to facilitate this process, allowing memory networks to be repeatedly reactivated in the absence of new sensory input. The process of memory reactivation and consolidation in the sleeping brain appears to influence conscious experience during sleep, contributing to dream content recalled on awakening. This article outlines several lines of evidence in support of this hypothesis, and responds to some common objections.

  10. Does abnormal sleep impair memory consolidation in schizophrenia?

    Directory of Open Access Journals (Sweden)

    Dara S Manoach

    2009-09-01

    Full Text Available Although disturbed sleep is a prominent feature of schizophrenia, its relation to the pathophysiology, signs, and symptoms of schizophrenia remains poorly understood. Sleep disturbances are well known to impair cognition in healthy individuals. Yet, in spite of its ubiquity in schizophrenia, abnormal sleep has generally been overlooked as a potential contributor to cognitive deficits. Amelioration of cognitive deficits is a current priority of the schizophrenia research community, but most efforts to define, characterize, and quantify cognitive deficits focus on cross-sectional measures. While this approach provides a valid snapshot of function, there is now overwhelming evidence that critical aspects of learning and memory consolidation happen offline, both over time and with sleep. Initial memory encoding is followed by a prolonged period of consolidation, integration, and reorganization, that continues over days or even years. Much of this evolution of memories is mediated by sleep. This article briefly reviews (i abnormal sleep in schizophrenia, (ii sleep-dependent memory consolidation in healthy individuals, (iii recent findings of impaired sleep-dependent memory consolidation in schizophrenia, and (iv implications of impaired sleep-dependent memory consolidation in schizophrenia. This literature suggests that abnormal sleep in schizophrenia disrupts attention and impairs sleep-dependent memory consolidation and task automation. We conclude that these sleep-dependent impairments may contribute substantially to generalized cognitive deficits in schizophrenia. Understanding this contribution may open new avenues to ameliorating cognitive dysfunction and thereby improve outcome in schizophrenia.

  11. Cooperation. An alternative to consolidation or bankruptcy.

    Science.gov (United States)

    Cady, G

    1994-04-01

    With all the recent consolidation and doomsaying within the EMS industry, the music from the movie "Jaws" is likely playing a constant refrain in the minds of many smaller EMS providers. The word from the consolidators--those large companies buying up small and midsized ambulance services--is that health maintenance organizations (HMOs) soon will be purchasing EMS and other "out-of-hospital" services and that since HMOs are for-profit institutions, they will be looking for the least expensive EMS delivery system. The consolidators and others with a stake in the new order assert that cost-effective services can only be produced by large national EMS companies; smaller companies will be left out in the cold. But will they?

  12. 17 CFR 240.16b-7 - Mergers, reclassifications, and consolidations.

    Science.gov (United States)

    2010-04-01

    ... financial statements for a 12 month period before the merger, reclassification or consolidation, or such..., and consolidations. 240.16b-7 Section 240.16b-7 Commodity and Securities Exchanges SECURITIES AND...) § 240.16b-7 Mergers, reclassifications, and consolidations. (a) The following transactions shall be...

  13. Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy.

    Science.gov (United States)

    Talamo, Giampaolo; Angtuaco, Edgardo; Walker, Ronald C; Dong, Li; Miceli, Marisa H; Zangari, Maurizio; Tricot, Guido; Barlogie, Bart; Anaissie, Elias

    2005-08-01

    To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy. A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period. With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones. AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

  14. Suitability of bovine bile compared to urine for detection of free, sulfate and glucuronate boldenone, androstadienedione, cortisol, cortisone, prednisolone, prednisone and dexamethasone by LC-MS/MS.

    Science.gov (United States)

    Chiesa, Luca; Nobile, Maria; Panseri, Sara; Vigo, Daniele; Pavlovic, Radmila; Arioli, Francesco

    2015-12-01

    The administration of boldenone and androstadienedione to cattle is forbidden in the European Union, while prednisolone is permitted for therapeutic purposes. They are pseudoendogenous substances (endogenously produced under certain circumstances). The commonly used matrices in control analyses are urine or liver. With the aim of improving the residue controls, we previously validated a method for steroid analysis in bile. We now compare urine (a 'classic' matrix) to bile, both collected at the slaughterhouse, to understand whether the detection of steroids in the latter is easier. With the aim of having clearer results, we tested the presence of the synthetic corticosteroid dexamethasone. The results show that bile does not substantially improve the detection of boldenone, or its conjugates, prednisolone and prednisone. Dexamethasone, instead, was found in 10 out of 53 bovine bile samples, but only in one urine sample from the same animals. Bile could constitute a novel matrix for the analysis of residues in food-producing animals, and possibly not only of synthetic corticosteroids. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Role of adult neurogenesis in hippocampal-cortical memory consolidation

    Science.gov (United States)

    2014-01-01

    Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

  16. Consistency based correlations for tailings consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Azam, S.; Paul, A.C. [Regina Univ., Regina, SK (Canada). Environmental Systems Engineering

    2010-07-01

    The extraction of oil, uranium, metals and mineral resources from the earth generates significant amounts of tailings slurry. The tailings are contained in a disposal area with perimeter dykes constructed from the coarser fraction of the slurry. There are many unique challenges pertaining to the management of the containment facilities for several decades beyond mine closure that are a result of the slow settling rates of the fines and the high standing toxic waters. Many tailings dam failures in different parts of the world have been reported to result in significant contaminant releases causing public concern over the conventional practice of tailings disposal. Therefore, in order to reduce and minimize the environmental footprint, the fluid tailings need to undergo efficient consolidation. This paper presented an investigation into the consolidation behaviour of tailings in conjunction with soil consistency that captured physicochemical interactions. The paper discussed the large strain consolidation behaviour (volume compressibility and hydraulic conductivity) of six fine-grained soil slurries based on published data. The paper provided background information on the study and presented the research methodology. The geotechnical index properties of the selected materials were also presented. The large strain consolidation, volume compressibility correlations, and hydraulic conductivity correlations were provided. It was concluded that the normalized void ratio best described volume compressibility whereas liquidity index best explained the hydraulic conductivity. 17 refs., 3 tabs., 4 figs.

  17. Bank Consolidation, Internationalization, and Conglomeration; Trends and Implications for Financial Risk

    OpenAIRE

    Gianni De Nicolo; Mary G Zephirin; Philip F. Bartholomew; Jahanara Zaman

    2003-01-01

    This paper documents global trends in bank activity, consolidation, internationalization, and financial firm conglomeration, and explores the extent to which financial firm risk and systemic risk potential in banking are related to consolidation and conglomeration. We find that while there is a substantial upward trend in conglomeration globally, consolidation and internationalization exhibit uneven patterns across world regions. Trends in consolidation and conglomeration indicate increased r...

  18. The CCCTB Concept of Consolidation and the Rules on Entering a Group

    NARCIS (Netherlands)

    van de Streek, J.

    2012-01-01

    The consolidation element is at the heart of the proposed Directive on a harmonized Common Consolidated Corporate Tax Base (CCCTB). In this article, the author examines the scope of the consolidation concept. When a company enters a consolidated group, conflicts of interest arise between Member

  19. Post-study caffeine administration enhances memory consolidation in humans.

    Science.gov (United States)

    Borota, Daniel; Murray, Elizabeth; Keceli, Gizem; Chang, Allen; Watabe, Joseph M; Ly, Maria; Toscano, John P; Yassa, Michael A

    2014-02-01

    It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans.

  20. Conceptual Design for Consolidation TCAP

    International Nuclear Information System (INIS)

    Klein, J.E.

    1999-01-01

    Two alternate Thermal Cycling Absorption Process (TCAP) designs have been developed for the Tritium Facility Modernization and Consolidation (TFM and C) Project. The alternate designs were developed to improve upon the existing Replacement Tritium Facility (RTF) TCAP design and to eliminate the use of building distributed hot and cold nitrogen system.A brief description of TCAP theory and modeling is presented, followed by an overview of the design criteria for the Isotope Separation System (ISS). Both designs are described in detail, along with a generic description of the complete TCAP system. A design is recommend for the Consolidation Project, and a development plan for both designs is proposed

  1. Reward Value Determines Memory Consolidation in Parasitic Wasps

    NARCIS (Netherlands)

    Kruidhof, H.M.; Pashalidou, F.G.; Fatouros, N.E.; Figueroa, I.A.; Vet, L.E.M.; Smid, H.M.; Huigens, M.E.

    2012-01-01

    Animals can store learned information in their brains through a series of distinct memory forms. Short-lasting memory forms can be followed by longer-lasting, consolidated memory forms. However, the factors determining variation in memory consolidation encountered in nature have thus far not been

  2. Task Classification Based Energy-Aware Consolidation in Clouds

    Directory of Open Access Journals (Sweden)

    HeeSeok Choi

    2016-01-01

    Full Text Available We consider a cloud data center, in which the service provider supplies virtual machines (VMs on hosts or physical machines (PMs to its subscribers for computation in an on-demand fashion. For the cloud data center, we propose a task consolidation algorithm based on task classification (i.e., computation-intensive and data-intensive and resource utilization (e.g., CPU and RAM. Furthermore, we design a VM consolidation algorithm to balance task execution time and energy consumption without violating a predefined service level agreement (SLA. Unlike the existing research on VM consolidation or scheduling that applies none or single threshold schemes, we focus on a double threshold (upper and lower scheme, which is used for VM consolidation. More specifically, when a host operates with resource utilization below the lower threshold, all the VMs on the host will be scheduled to be migrated to other hosts and then the host will be powered down, while when a host operates with resource utilization above the upper threshold, a VM will be migrated to avoid using 100% of resource utilization. Based on experimental performance evaluations with real-world traces, we prove that our task classification based energy-aware consolidation algorithm (TCEA achieves a significant energy reduction without incurring predefined SLA violations.

  3. Resting state EEG correlates of memory consolidation.

    Science.gov (United States)

    Brokaw, Kate; Tishler, Ward; Manceor, Stephanie; Hamilton, Kelly; Gaulden, Andrew; Parr, Elaine; Wamsley, Erin J

    2016-04-01

    Numerous studies demonstrate that post-training sleep benefits human memory. At the same time, emerging data suggest that other resting states may similarly facilitate consolidation. In order to identify the conditions under which non-sleep resting states benefit memory, we conducted an EEG (electroencephalographic) study of verbal memory retention across 15min of eyes-closed rest. Participants (n=26) listened to a short story and then either rested with their eyes closed, or else completed a distractor task for 15min. A delayed recall test was administered immediately following the rest period. We found, first, that quiet rest enhanced memory for the short story. Improved memory was associated with a particular EEG signature of increased slow oscillatory activity (rest can facilitate memory, and that this may occur via an active process of consolidation supported by slow oscillatory EEG activity and characterized by decreased attention to the external environment. Slow oscillatory EEG rhythms are proposed to facilitate memory consolidation during sleep by promoting hippocampal-cortical communication. Our findings suggest that EEG slow oscillations could play a significant role in memory consolidation during other resting states as well. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. SOME ASPECTS REGARDING THE THEORIES OF CONSOLIDATED FINANCIAL STATEMENTS

    Directory of Open Access Journals (Sweden)

    Carmen NISTOR

    2015-04-01

    Full Text Available Although accounts consolidation was used in practice from the early 1900’s its theoretical basis were developed later in concordance with the rise of concepts like “entity” and “group”. The aim of this article is to examine the literature in the accounting field regarding the consolidation theories developed over the years. In order to discuss the different opinions regarding the consolidation theories we used the descriptive approach. As a result we tried to explain how these theories appeared and developed, respectively what consequences have their use in preparing consolidated financial statements. The results of the study suggest that every theory has certain aspects which differentiate it from the others in terms of recognition of subsidiary income and reporting net assets of the subsidiary. However, from all theories analyzed, the entity theory takes into account several guidelines of maximum importance when preparing consolidated financial statements: “You can’t own yourself!”, “You can’t owe yourself money!”, “You can’t make money selling to yourself.”

  5. Sleep-dependent memory consolidation in patients with sleep disorders.

    Science.gov (United States)

    Cipolli, Carlo; Mazzetti, Michela; Plazzi, Giuseppe

    2013-04-01

    Sleep can improve the off-line memory consolidation of new items of declarative and non-declarative information in healthy subjects, whereas acute sleep loss, as well as sleep restriction and fragmentation, impair consolidation. This suggests that, by modifying the amount and/or architecture of sleep, chronic sleep disorders may also lead to a lower gain in off-line consolidation, which in turn may be responsible for the varying levels of impaired performance at memory tasks usually observed in sleep-disordered patients. The experimental studies conducted to date have shown specific impairments of sleep-dependent consolidation overall for verbal and visual declarative information in patients with primary insomnia, for verbal declarative information in patients with obstructive sleep apnoeas, and for visual procedural skills in patients with narcolepsy-cataplexy. These findings corroborate the hypothesis that impaired consolidation is a consequence of the chronically altered organization of sleep. Moreover, they raise several novel questions as to: a) the reversibility of consolidation impairment in the case of effective treatment, b) the possible negative influence of altered prior sleep also on the encoding of new information, and c) the relationships between altered sleep and memory impairment in patients with other (medical, psychiatric or neurological) diseases associated with quantitative and/or qualitative changes of sleep architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Memory Consolidation and Gene Expression in "Periplaneta Americana"

    Science.gov (United States)

    Strausfeld, Nicholas J.; Pinter, Marianna; Lent, David D.

    2005-01-01

    A unique behavioral paradigm has been developed for "Periplaneta americana" that assesses the timing and success of memory consolidation leading to long-term memory of visual-olfactory associations. The brains of trained and control animals, removed at the critical consolidation period, were screened by two-directional suppression subtractive…

  7. A unified theory for systems and cellular memory consolidation.

    Science.gov (United States)

    Dash, Pramod K; Hebert, April E; Runyan, Jason D

    2004-04-01

    The time-limited role of the hippocampus for explicit memory storage has been referred to as systems consolidation where learning-related changes occur first in the hippocampus followed by the gradual development of a more distributed memory trace in the neocortex. Recent experiments are beginning to show that learning induces plasticity-related molecular changes in the neocortex as well as in the hippocampus and with a similar time course. Present memory consolidation theories do not account for these findings. In this report, we present a theory (the C theory) that incorporates these new findings, provides an explanation for the length of time for hippocampal dependency, and that can account for the apparent longer consolidation periods in species with larger brains. This theory proposes that a process of cellular consolidation occurs in the hippocampus and in areas of the neocortex during and shortly after learning resulting in long-term memory storage in both areas. For a limited time, the hippocampus is necessary for memory retrieval, a process involving the coordinated reactivation of these areas. This reactivation is later mediated by longer extrahippocampal connectivity between areas. The delay in hippocampal-independent memory retrieval is the time it takes for gene products in these longer extrahippocampal projections to be transported from the soma to tagged synapses by slow axonal transport. This cellular transport event defines the period of hippocampal dependency and, thus, the duration of memory consolidation. The theoretical description for memory consolidation presented in this review provides alternative explanations for several experimental observations and presents a unification of the concepts of systems and cellular memory consolidation.

  8. THE FORMATION OF INSTITUTIONAL ENVIRONMENT OF AGRICULTURAL LAND CONSOLIDATION IN UKRAINE

    Directory of Open Access Journals (Sweden)

    Andriy Popov

    2015-11-01

    Full Text Available Every theory requires an application tool. Land consolidation is the multidisciplinary tool for sustainable rural development with its dynamic structure that gives possibilities getting the best solutions for land management decision. That is why the main purpose of the article is a theoretical study and development of scientific and practical recommendations concerning the formation of institutional environment of agricultural land consolidation in Ukraine. The subject of study is the formation of agricultural land consolidation. Methodology. The study used the following methods: dialectical, logical and abstract, system analysis (theoretical and methodological generalizations, defining the essence of the content of institutional environment of agricultural land consolidation. This paper identifies the role of the institutions in economic development and characterised the regulatory, procedural, distributive, informational, development and accumulation functions of agricultural land consolidation institution. As a novelty items offered and provided the detailed description of the main components of the institutional environment of agricultural land consolidation such as: traditional and mental, legal, causal, organizational and structural, and procedural. The essence of institutions of each of these components and their meaning and relationships are presented. Theoretically investigated that the formation of institutional mechanism of consolidation should be a symbiosis of both traditional and market institutions based on democratic principles under community participation. The article focuses on the feasibility of the formation of mechanism for monitoring the effectiveness of institutions. As the result of the study the author proposed to consider the institutional environment of agricultural land consolidation as a regulatory system harmonizing relations of the agricultural production, social and natural resources, designed to optimize the

  9. SOME ASPECTS REGARDING THE THEORIES OF CONSOLIDATED FINANCIAL STATEMENTS

    OpenAIRE

    Carmen NISTOR

    2015-01-01

    Although accounts consolidation was used in practice from the early 1900’s its theoretical basis were developed later in concordance with the rise of concepts like “entity” and “group”. The aim of this article is to examine the literature in the accounting field regarding the consolidation theories developed over the years. In order to discuss the different opinions regarding the consolidation theories we used the descriptive approach. As a result we tried to explain how these theories appear...

  10. Investigations of the microbial transformation of cortisol to prednisolone in urine samples.

    Science.gov (United States)

    Bredehöft, Michael; Baginski, Rainer; Parr, Maria-Kristina; Thevis, Mario; Schänzer, Wilhelm

    2012-03-01

    Doping control samples are normally collected under non-sterile conditions and sometimes, storage and transportation are influenced by parameters such as the temperature. Therefore, microbial contamination and subsequent alteration of a sample's composition are possible. Studies regarding sample collection in cattle breeding have already shown enzymatic transformation of endogenous testosterone to boldenone causing false-positive findings. The aim of the present study was to investigate whether positive doping cases with the synthetic corticosteroids prednisolone and prednisone may result from microbial transformation of the endogenous corticosteroids cortisol and cortisone, respectively. A method comprising parameters such as pH values and screening results for synthetic glucocorticosteroids as well as incubation experiments followed by liquid chromatographic and mass spectrometric analysis was employed to test for contaminating germs with Δ(1)-dehydrogenase activity. Over 700 urine samples comprising inpatient and doping control specimens were investigated. In none of them, 1,2-dehydrogenating activity was confirmed. These findings are in accordance with other studies. However, the problem of microbial alteration of doping control specimens with special respect to 1,2-dehydrogenation must not be underestimated. Article from a special issue on steroids and microorganisms. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Consolidation Theory for a Stone Column Composite Foundation under Multistage Loading

    OpenAIRE

    Huang, Shenggen; Feng, Yingtao; Liu, Hao; Wu, Wenbing; Mei, Guoxiong

    2016-01-01

    The consolidation theories considering instant load cannot fully reveal the consolidation mechanism of a stone column composite foundation used in the expressway embankments due to the time effect of loading; that is, the expressway embankments are often constructed in several stages for a long time. Meanwhile, owing to the special property that the pile-soil stress ratio is larger than 1, the consolidation theory for sand drain well foundation cannot be used directly in the consolidation ana...

  12. Differential effects of non-REM and REM sleep on memory consolidation?

    Science.gov (United States)

    Ackermann, Sandra; Rasch, Björn

    2014-02-01

    Sleep benefits memory consolidation. Previous theoretical accounts have proposed a differential role of slow-wave sleep (SWS), rapid-eye-movement (REM) sleep, and stage N2 sleep for different types of memories. For example the dual process hypothesis proposes that SWS is beneficial for declarative memories, whereas REM sleep is important for consolidation of non-declarative, procedural and emotional memories. In fact, numerous recent studies do provide further support for the crucial role of SWS (or non-REM sleep) in declarative memory consolidation. However, recent evidence for the benefit of REM sleep for non-declarative memories is rather scarce. In contrast, several recent studies have related consolidation of procedural memories (and some also emotional memories) to SWS (or non-REM sleep)-dependent consolidation processes. We will review this recent evidence, and propose future research questions to advance our understanding of the role of different sleep stages for memory consolidation.

  13. A cold demonstration of fuel consolidation. Part 1

    International Nuclear Information System (INIS)

    Matheson, J.E.

    1989-01-01

    Spent fuel consolidation is an option for increasing spent fuel storage capacities being considered by many utilities. The process of consolidating fuel involves separating the fuel rods from the structural frame which holds them in a square array. The rods are then repackaged into a tightly packed bundle which occupies about half the cross-sectional area of fuel assembly. Thus approximately twice as much fuel can be stored in the underwater racks at a spent fuel storage pool. There have been several demonstrations of fuel consolidation to date. The focus of this paper is the development and subsequent demonstration program of a shear/compactor

  14. Method for consolidating incompetent formations

    Energy Technology Data Exchange (ETDEWEB)

    Pavlich, J.P.; Calvert, D.G.

    1965-02-23

    An incompetent formation is consolidated and left permeable by first injecting a solidifiable liquid resin, and following this by an organic liquid to set the resin. The liquid resin used may be 3 (glycidyloxy) propyl trimethoxysilane in sufficient concentration to considerably increase the compressive strength of the consolidated zone. The silane may be used in a ratio of between 0.5 and 5% of the total volume of the liquid resin. The liquid resin used may be a phenol-formaldehyde condensation product dispersed in an aliphatic alcohol with from 1 to 4 carbon atoms. The liquid resin used may be an epoxy containing a hardener. The resin may be displaced into the formation by a liquid hydrocarbon. (5 claims)

  15. To Replay, Perchance to Consolidate.

    Directory of Open Access Journals (Sweden)

    Lisa Genzel

    2015-10-01

    Full Text Available After a memory is formed, it continues to be processed by the brain. These "off-line" processes consolidate the memory, leading to its enhancement and to changes in memory circuits. Potentially, these memory changes are driven by off-line replay of the pattern of neuronal activity present when the memory was being formed. A new study by Dhaksin Ramanathan and colleagues, published in PLOS Biology, demonstrates that replay occurs predominately after the acquisition of a new motor skill and that it is related to changes in memory performance and to the subsequent changes in memory circuits. Together, these observations reveal the importance of neuronal replay in the consolidation of novel motor skills.

  16. Accounting Treatment for Separate and Consolidated Financial Statements

    Directory of Open Access Journals (Sweden)

    Iuliana Oana Mihai

    2015-09-01

    Full Text Available The rules governing the financial statements consolidation have been subject for debates for many years. The financial crisis in 2008 accelerated changes toward new improved standards. The main objective of this article is to explain the key parts of the IASB standards for consolidation of financial statements.

  17. 12 CFR 931.5 - Liquidation, merger, or consolidation.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Liquidation, merger, or consolidation. 931.5 Section 931.5 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK RISK MANAGEMENT AND CAPITAL STANDARDS FEDERAL HOME LOAN BANK CAPITAL STOCK § 931.5 Liquidation, merger, or consolidation. The...

  18. Healthcare mergers and acquisitions: strategies for consolidation.

    Science.gov (United States)

    Zuckerman, Alan M

    2011-01-01

    The passage of federal healthcare reform legislation, in combination with other factors, makes it likely that the next few years will be a major period of consolidation for healthcare organizations. This article examines the seven key forces reshaping healthcare delivery--from insurance industry consolidation to cost inflation to the increasing gap between financially strong and struggling providers--and provides advice for organizations on both sides of an acquisition.

  19. SOME DISCLOSURE ASPECTS REGARDING CONSOLIDATED FINANCIAL STATEMENTS

    OpenAIRE

    Cirstea Andreea; Baltariu Carmen-Alexandra

    2013-01-01

    The purpose of this article is to analyze the current state of consolidated reporting practice harmonization concerning the choice of presenting the income statement, the changes in equity, the methods used for presenting the cash flow statement, the extant methods for evaluating and reporting goodwill, the extant methods in which jointly controlled entities are accounted in the consolidated financial statements, or the choice for recognizing investments in subsidiaries, jointly controlled en...

  20. Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

    Directory of Open Access Journals (Sweden)

    Andersson Eva

    2009-02-01

    Full Text Available Abstract Background Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation. Methods This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid was compared with prednisolone (30 mg once daily plus inhaled formoterol (9 μg bid in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV1 30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home. A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV1 45% of predicted were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid for another 12 weeks. Change in FEV1 was the primary efficacy variable. Non-inferiority was predefined. Results Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV1-change (97.5% CI was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up did not differ between the groups. No safety concerns were identified. Conclusion High dose budesonide

  1. Consolidation Theory for a Stone Column Composite Foundation under Multistage Loading

    Directory of Open Access Journals (Sweden)

    Shenggen Huang

    2016-01-01

    Full Text Available The consolidation theories considering instant load cannot fully reveal the consolidation mechanism of a stone column composite foundation used in the expressway embankments due to the time effect of loading; that is, the expressway embankments are often constructed in several stages for a long time. Meanwhile, owing to the special property that the pile-soil stress ratio is larger than 1, the consolidation theory for sand drain well foundation cannot be used directly in the consolidation analysis of stone column composite foundation. Based on the principle that the vertical load applied on the composite foundation is shared by the stone column and the surrounding soil, the governing solutions for the stone column composite foundation under a multistage load are established. By virtue of the separation of variables, the corresponding solutions of degree of consolidation for loading stage and maintaining load stage are derived separately. According to the Carrillo theorem, the solution for the average total degree of consolidation of entire composite foundation is also obtained. Finally, the reasonableness of the present solution has been verified by comparing the consolidation curve calculated by the present solution with that measured by site test.

  2. Success Modulates Consolidation of a Visuomotor Adaptation Task

    Science.gov (United States)

    Trempe, Maxime; Sabourin, Maxime; Proteau, Luc

    2012-01-01

    Consolidation is a time-dependent process that is responsible for the storage of information in long-term memory. As such, it plays a crucial role in motor learning. Prior research suggests that some consolidation processes are triggered only when the learner experiences some success during practice. In the present study, we tested whether…

  3. Consolidated Copayment Processing Center (CCPC)

    Data.gov (United States)

    Department of Veterans Affairs — The Consolidated Copayment Processing Center (CCPC) database contains Veteran patient contact and billing information in order to support the printing and mailing of...

  4. How aging affects sleep-dependent memory consolidation?

    Directory of Open Access Journals (Sweden)

    Caroline eHarand

    2012-02-01

    Full Text Available Sleep plays multiple functions among which energy conservation or recuperative processes. Besides, growing evidence indicate that sleep plays also a major role in memory consolidation, a process by which recently acquired and labile memory traces are progressively strengthened into more permanent and/or enhanced forms. Indeed, memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, which is favoured by the neurochemical environment and the electrophysiological activity observed during sleep. Two putative, probably not exclusive, models (hippocampo-neocortical dialogue and synaptic homeostasis hypothesis have been proposed to explain the beneficial effect of sleep on memory processes. It is worth noting that all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults.Here, we give an overview of the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.

  5. COST IMPACT OF ROD CONSOLIDATION ON THE VIABILITY ASSESSMENT DESIGN

    International Nuclear Information System (INIS)

    D. Lancaster

    1999-01-01

    The cost impact to the Civilian Radioactive Waste Management System of using rod consolidation is evaluated. Previous work has demonstrated that the fuel rods of two assemblies can be packed into a canister that can fit into the same size space as that used to store a single assembly. The remaining fuel assembly hardware can be compacted into the same size canisters with a ratio of 1 hardware canister per each 6 to 12 assemblies. Transportation casks of the same size as currently available can load twice the number of assemblies by placing the compacted assemblies in the slots currently designed for a single assembly. Waste packages similarly could contain twice the number of assemblies; however, thermal constraints would require considering either a low burnup or cooling. The analysis evaluates the impact of rod consolidation on CRWMS costs for consolidation at prior to transportation and for consolidation at the Monitored Geological Repository surface facility. For this study, no design changes were made to either the transport casks or waste packages. Waste package designs used for the Viability Assessment design were employed but derated to make the thermal limits. A logistics analysis of the waste was performed to determine the number of each waste package with each loading. A review of past rod consolidation experience found cost estimates which range from $10/kgU to $32/kgU. $30/kgU was assumed for rod consolidation costs prior to transportation. Transportation cost savings are about $17/kgU and waste package cost savings are about $21/kgU. The net saving to the system is approximately $500 million if the consolidation is performed prior to transportation. If consolidation were performed at the repository surface facilities, it would cost approximately $15/kgU. No transportation savings would be realized. The net savings for consolidation at the repository site would be about $400 million dollars

  6. Consolidation and restoration of memory traces in working memory.

    Science.gov (United States)

    De Schrijver, Sébastien; Barrouillet, Pierre

    2017-10-01

    Consolidation is the process through which ephemeral sensory traces are transformed into more stable short-term memory traces. It has been shown that consolidation plays a crucial role in working memory (WM) performance, by strengthening memory traces that then better resist interference and decay. In a recent study, Bayliss, Bogdanovs, and Jarrold (Journal of Memory and Language, 81, 34-50, 2015) argued that this process is separate from the processes known to restore WM traces after degradation, such as attentional refreshing and verbal rehearsal. In the present study, we investigated the relationship between the two types of processes in the context of WM span tasks. Participants were presented with series of letters for serial recall, each letter being followed by four digits for parity judgment. Consolidation opportunity was manipulated by varying the delay between each letter and the first digit to be processed, while opportunities for restoration were manipulated by varying the pace at which the parity task had to be performed (i.e., its cognitive load, or CL). Increasing the time available for either consolidation or restoration resulted in higher WM spans, with some substitutability between the two processes. Accordingly, when consolidation time was added to restoration time in the calculation of CL, the new resulting index, called extended CL, proved a very good predictor of recall performance, a finding also observed when verbal rehearsal was prevented by articulatory suppression. This substitutability between consolidation and restoration suggests that both processes may rely on the same mechanisms.

  7. A consolidated and standardized relational database for ER data

    International Nuclear Information System (INIS)

    Zygmunt, B.C.

    1995-01-01

    The three US Department of Energy (DOE) installations on the Oak Ridge Reservation (ORR) (Oak Ridge National Laboratory, Y-12, and K-25) were established during World War II as part of the Manhattan Project that ''built the bomb.'' That research, and work in more recent years, has resulted in the generation of radioactive materials and other toxic wastes. Lockheed Martin Energy Systems manages the three Oak Ridge installations (as well as the Environmental Restoration (ER) programs at the DOE plants in Portsmouth, Ohio, and Paducah, Kentucky). DOE Oak Ridge Operations has been mandated by federal and state agreements to provide a consolidated repository of environmental data and is tasked to support environmental data management activities at all five installations. The Oak Ridge Environmental Information System (OREIS) was initiated to fulfill these requirements. The primary use of OREIS data is to provide access to project results by regulators. A secondary use is to serve as background data for other projects. This paper discusses the benefits of a consolidated and standardized database; reasons for resistance to the consolidation of data; implementing a consolidated database, including attempts at standardization, deciding what to include in the consolidated database, establishing lists of valid values, and addressing quality control (QC) issues; and the evolution of a consolidated database, which includes developing and training a user community, dealing with configuration control issues, and incorporating historical data. OREIS is used to illustrate these topics

  8. Consolidated results 2000. Forecasts 2001; Resultats consolides 2000. Perspectives 2001

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This document presents an economic analysis of the Group Gaz De France consolidated results for the year 2000. The main topics are the evolution of the energy market, the great economic growth for the five businesses of the Group (exploration-production, trade, transport, distribution and services), financial results affected by the supply costs increase, the position reinforcement among the gas leaders in Europe and the highlights of 2000. (A.L.B.)

  9. Relation Between Filtration and Soil Consolidation Theories

    OpenAIRE

    Strzelecki Tomasz; Strzelecki Michał

    2015-01-01

    This paper presents a different, than commonly used, form of equations describing the filtration of a viscous compressible fluid through a porous medium in isothermal conditions. This mathematical model is compared with the liquid flow equations used in the theory of consolidation. It is shown that the current commonly used filtration model representation significantly differs from the filtration process representation in Biot’s and Terzaghi’s soil consolidation models, which has a bearing on...

  10. Saskatchewan Energy Holdings Ltd. consolidated financial statements

    International Nuclear Information System (INIS)

    1991-01-01

    The consolidated financial statements of Saskatchewan Energy Holdings Ltd. (formerly Saskatchewan Energy Corporation) as of December 31, 1990, and the consolidated statements of earnings and retained earnings and changes in cash position for the year are presented. Data include an inventory of supplies, natural gas in storage, property, plant and equipment. Financial statements are also presented for the year ending December 31, 1989, with comparative figures for the seven months ending December 31, 1988

  11. Saskatchewan Energy Holdings Ltd. consolidated financial statements

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    The consolidated financial statements of Saskatchewan Energy Holdings Ltd. (formerly Saskatchewan Energy Corporation) as of December 31, 1990, and the consolidated statements of earnings and retained earnings and changes in cash position for the year are presented. Data include an inventory of supplies, natural gas in storage, property, plant and equipment. Financial statements are also presented for the year ending December 31, 1989, with comparative figures for the seven months ending December 31, 1988.

  12. Mechanisms of Social Consolidation in the Network Society

    Directory of Open Access Journals (Sweden)

    Lidia A. Bobova

    2014-01-01

    Full Text Available During the last five years the world has seen the emergence of mass global and regional social movements outside of institutional structures representing open systems with a spontaneous nature. These social movements do not have any tangible hierarchy and leaders; information within the movement activity is spread virally and mainly using new electronic communication tools - namely, mass self-communication constituting spaces of communication autonomy beyond the control of governments. A feature of the new type of social movements is their emergence in virtual space. Such mass movements manifest intensified consolidation processes in the modern society - due to fundamentally new factors. New practical mechanisms of consolidation amid an increase in the proportion of young people in countries are directly linked with technological developments that influenced in essence communication and changes in the established modern informational society. Virtual mass self-communication becomes the main practical mechanism for social consolidation in the modern informational society. The consolidation process intensifies due to government legitimacy crisis and loss of public trust in government and indicates an emergence of a new form of a civil society.

  13. Failure envelope approach for consolidated undrained capacity of shallow foundations

    OpenAIRE

    Vulpe, Cristina; Gourvenec, Susan; Leman, Billy; Fung, Kah Ngii

    2016-01-01

    A generalized framework is applied to predict consolidated undrained VHM failure envelopes for surface circular and strip foundations. The failure envelopes for consolidated undrained conditions are shown to be scaled from those for unconsolidated undrained conditions by the uniaxial consolidated undrained capacities, which are predicted through a theoretical framework based on fundamental critical state soil mechanics. The framework is applied to results from small-strain finite-element anal...

  14. Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives.

    Science.gov (United States)

    Meyring, M; Chankvetadze, B; Blaschke, G

    1999-09-01

    The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied in capillary electrophoresis (CE) using four different randomly substituted charged cyclodextrin (CD) derivatives, the combinations of some of them with each other, and beta-CD. TD, as well as two metabolites recently found in incubations of human liver microsomes and human blood, 5-hydroxythalidomide (5-OH-TD) and one of the diastereomeric 5'-hydroxythalidomides (5'-OH-TD), are neutral compounds. Therefore, they were resolved using charged chiral selectors in CE. Two different separation modes (normal polarity and carrier mode) and two different capillaries (fused-silica and polyacrylamide-coated) were tested. Based on the behavior of the individual CDs, their designed combinations were selected in order to improve the separation selectivity and enantioselectivity. Under optimized conditions all three chiral compounds and their enantiomers were resolved simultaneously.

  15. The Consolidated Net Worth of Private Colleges. Recommendation of a Model.

    Science.gov (United States)

    Jenny, Hans H.

    One of several essential tools for assessing how the financial health of educational institutions is evolving is the Consolidated Net Worth Statement. This essay explores various aspects of conventional "funds" balance sheets and compares them with the Consolidated Net Worth. Emphasis is placed on how the Consolidated Net Worth Statement…

  16. Land consolidation in mountain areas. Case study from southern Poland

    Science.gov (United States)

    Janus, Jarosław; Łopacka, Magdalena; John, Ewa

    2017-12-01

    Land consolidation procedures are an attempt to comprehensively change the existing spatial structure of land in rural areas. This treatment also brings many other social and economic benefi ts, contributing to the development of consolidated areas. Land consolidation in mountain areas differs in many respects from those implemented in areas with more favorable conditions for the functioning of agriculture. The unfavorable values of land fragmentation indices, terrain conditions and lower than the average soil quality affect both the dominant forms of agricultural activity and the limited opportunities to improve the distribution of plots in space, parameters of shape, and the area as a result of land consolidation. For this reason, the effectiveness of land consolidation in mountain areas can be achieved by improving the quality of transportation network and the accessibility of the plots, arranging ownership issues and improving the quality of cadastral documentation. This article presents the evaluation of the measures of effectiveness of land consolidation realized in mountain areas on the example of Łetownia Village in the Małopolska Province, located in the southern part of Poland. Selected village is an area with unfavorable conditions for the functioning of agriculture and high values of land fragmentation indices.

  17. Land consolidation in mountain areas. Case study from southern Poland

    Directory of Open Access Journals (Sweden)

    Janus Jarosław

    2017-12-01

    Full Text Available Land consolidation procedures are an attempt to comprehensively change the existing spatial structure of land in rural areas. This treatment also brings many other social and economic benefi ts, contributing to the development of consolidated areas. Land consolidation in mountain areas differs in many respects from those implemented in areas with more favorable conditions for the functioning of agriculture. The unfavorable values of land fragmentation indices, terrain conditions and lower than the average soil quality affect both the dominant forms of agricultural activity and the limited opportunities to improve the distribution of plots in space, parameters of shape, and the area as a result of land consolidation. For this reason, the effectiveness of land consolidation in mountain areas can be achieved by improving the quality of transportation network and the accessibility of the plots, arranging ownership issues and improving the quality of cadastral documentation. This article presents the evaluation of the measures of effectiveness of land consolidation realized in mountain areas on the example of Łetownia Village in the Małopolska Province, located in the southern part of Poland. Selected village is an area with unfavorable conditions for the functioning of agriculture and high values of land fragmentation indices.

  18. How long can austerity persist? The factors that sustain fiscal consolidations

    Directory of Open Access Journals (Sweden)

    David Lodge

    2013-06-01

    Full Text Available To put public debt on a sustainable path, many governments face the task of enacting large fiscal consolidation followed by years of sustained primary surpluses. By estimating hazard functions for the duration of consolidations, we analyse the features of past consolidation efforts across a panel of advanced economies. Our contribution is to identify the factors that help to start and sustain consolidations, separately discussing governments’ “commitment” to the cause as well as their “capacity” for action. Our analysis suggests that longer consolidations are initiated when public debt is high, fiscal deficits are large, the interest burden heavy and long-term sovereign bond yields elevated. However, we also find that a countries’ “capacity” to change course is important. Higher initial private sector savings, a stronger external balance, a competitive position and stable financial conditions appear to provide more scope for governments to sustain longer-lasting consolidations. Once we have controlled for the initial macroeconomic conditions, there is a lesser role for governments’ commitment as reflected in factors such as the composition and the pace of the fiscal adjustment or the political cycle in explaining the duration of consolidation. However, commitment to permanent, rather than temporary, fiscal adjustment is key.

  19. Impaired memory consolidation in children with obstructive sleep disordered breathing.

    Directory of Open Access Journals (Sweden)

    Kiran Maski

    Full Text Available Memory consolidation is stabilized and even enhanced by sleep (and particularly by 12-15 Hz sleep spindles in NREM stage 2 sleep in healthy children but it is unclear what happens to these processes when sleep is disturbed by obstructive sleep disordered breathing. This cross-sectional study investigates differences in declarative memory consolidation among children with primary snoring (PS and obstructive sleep apnea (OSA compared to controls. We further investigate whether memory consolidation group differences are associated with NREM stage 2 (N2 sigma (12-15 Hz or NREM slow oscillation (0.5-1 Hz spectral power bands. In this study, we trained and tested participants on a spatial declarative memory task with cued recall. Retest occurred after a period of daytime wake (Wake or a night of sleep (Sleep with in-lab polysomnography. 36 participants ages 5-9 years completed the protocol: 14 with OSA as defined by respiratory disturbance index (RDI > 1/hour, 12 with primary snoring (PS and 10 controls. OSA participants had poorer overall memory consolidation than controls across Wake and Sleep conditions [OSA: mean = -18.7% (5.8, controls: mean = 1.9% (7.2, t = -2.20, P = 0.04]. In contrast, PS participants and controls had comparable memory consolidation across conditions (t = 0.41; P = 0.38. We did not detect a main effect for condition (Sleep, Wake or group x condition interaction on memory consolidation. OSA participants had lower N2 sigma power than PS (P = 0.03 and controls (P = 0.004 and N2 sigma power inversely correlated with percentage of time snoring on the study night (r = -0.33, P<0.05. Across all participants, N2 sigma power modestly correlated with memory consolidation in both Sleep (r = 0.37, P = 0.03 and Wake conditions (r = 0.44, P = 0.009. Further observed variable path analysis showed that N2 sigma power mediated the relationship between group and mean memory consolidation across Sleep and Wake states [Bindirect = 6.76(3.5, z = 2

  20. Nicotine facilitates memory consolidation in perceptual learning.

    Science.gov (United States)

    Beer, Anton L; Vartak, Devavrat; Greenlee, Mark W

    2013-01-01

    Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Thermal Consolidation of Dredge Sand for Artificial Reef Formations

    Science.gov (United States)

    Trevino, Alexandro

    Coral Reef ecosystems have degraded over years due to a variety of environmental issues such as ocean acidification. The continuous stress has detrimental effects on coral reef ecosystems that can possibly lead to the loss of the ecosystem. Our research aims to construct a prototype of an artificial reef by consolidating dredge sand from the ship channels of South Texas. Consolidation is achieved through an aluminum polytetrafluoroethylene self-propagating high temperature process that yields a solid formation to mimic the physical properties of coral reef structures. Using thermodynamic calculations, the variation of initial components was determined that reached an adiabatic temperature with a maximum peak of 2000 K. The self-sustaining reaction front was obtained to rigidly consolidate the dredge sand only at composition concentrations exceeding a critical value of 24 wt.% Al, and 3 wt.% PTFE. The combustion synthesis produced a consolidated formation with a hardened and porous structure.

  2. Evidence for parallel consolidation of motion direction and orientation into visual short-term memory.

    Science.gov (United States)

    Rideaux, Reuben; Apthorp, Deborah; Edwards, Mark

    2015-02-12

    Recent findings have indicated the capacity to consolidate multiple items into visual short-term memory in parallel varies as a function of the type of information. That is, while color can be consolidated in parallel, evidence suggests that orientation cannot. Here we investigated the capacity to consolidate multiple motion directions in parallel and reexamined this capacity using orientation. This was achieved by determining the shortest exposure duration necessary to consolidate a single item, then examining whether two items, presented simultaneously, could be consolidated in that time. The results show that parallel consolidation of direction and orientation information is possible, and that parallel consolidation of direction appears to be limited to two. Additionally, we demonstrate the importance of adequate separation between feature intervals used to define items when attempting to consolidate in parallel, suggesting that when multiple items are consolidated in parallel, as opposed to serially, the resolution of representations suffer. Finally, we used facilitation of spatial attention to show that the deterioration of item resolution occurs during parallel consolidation, as opposed to storage. © 2015 ARVO.

  3. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation.

    Science.gov (United States)

    Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

    2017-01-01

    Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5-4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC) have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent) memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation). Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

  4. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Daisuke Miyamoto

    2017-11-01

    Full Text Available Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow waves can enhance or impair memory consolidation. During slow wave sleep, inter-areal interactions between the cortex and hippocampus (HC have been proposed to consolidate declarative memory; however, interactions for non-declarative (HC-independent memory remain largely uninvestigated. We recently showed that the directional influence in a slow-wave range through a top-down cortical long-range circuit is involved in the consolidation of non-declarative memory. At the synaptic level, the average cortical synaptic strength is known to be potentiated during wakefulness and depressed during sleep. Moreover, learning causes plasticity in a subset of synapses, allocating memory to them. Sleep may help to differentiate synaptic strength between allocated and non-allocated synapses (i.e., improving the signal-to-noise ratio, which may facilitate memory consolidation. Herein, we offer perspectives on inter-areal interactions and synaptic plasticity for memory consolidation during sleep.

  5. Effect of Oral Prednisolone on Symptom Duration and Severity in Nonasthmatic Adults With Acute Lower Respiratory Tract Infection: A Randomized Clinical Trial.

    Science.gov (United States)

    Hay, Alastair D; Little, Paul; Harnden, Anthony; Thompson, Matthew; Wang, Kay; Kendrick, Denise; Orton, Elizabeth; Brookes, Sara T; Young, Grace J; May, Margaret; Hollinghurst, Sandra; Carroll, Fran E; Downing, Harriet; Timmins, David; Lafond, Natasher; El-Gohary, Magdy; Moore, Michael

    2017-08-22

    Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence. To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma. Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years. Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days. The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events. Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, -0.20; 95% CI, -0.40 to 0.00; P = .05

  6. Preliminary design report: Prototypical Spent Fuel Consolidation Equipment Demonstration Project: Phase 1

    International Nuclear Information System (INIS)

    Blissell, W.H.; Ciez, A.P.; Mitchell, J.L.; Winkler, C.J.

    1986-12-01

    This document describes the Westinghouse Preliminary Design for the Prototypical Consolidation Demonstration Project per Department of Energy (DOE) Contract No. DE-AC07-86ID12649 and under direction of the DOE Idaho Operations Office. The preliminary design is the first step to providing the Department of Energy with a fully qualified, licensable, cost-effective spent fuel rod consolidation system. The design was developed using proven technologies and equipment to create an innovative approach to previous rod consolidation concepts. These innovations will better enable the Westinghouse system to: consolidate fuel rods in a precise, fully-controlled, accountable manner; package all rods from two PWR fuel assemblies or from four BWR fuel assemblies in one 8.5 inch square consolidated rods canister; meet all functional requirements; operate with all fuel types common to the US commercial nuclear industry with minimal tooling changeouts; and meet consolidation production process rates, while maintaining operator and public health and safety. This Preliminary Design Report provides both detailed descriptions of the equipment required to perform the rod consolidation process and the supporting analyses to validate the design

  7. Simulation and video software development for soil consolidation testing

    NARCIS (Netherlands)

    Karim, Usama F.A.

    2003-01-01

    The development techniques and file structures of CTM, a novel multi-media (computer simulation and video) package on consolidation and laboratory consolidation testing, are presented in this paper. A courseware tool called Authorware proved to be versatile for building the package and the paper

  8. Consolidated Financial Statements – in IAS 27 perspective

    Directory of Open Access Journals (Sweden)

    Mihai Deju

    2012-12-01

    Full Text Available The aspects concerning the preparation and publication of the consolidated financial statements have been the subject of the settlement by the Committee for International Accounting Standards (IAS even since 1976 with the publication of IAS 3 “Consolidated financial statements”. Subsequently, the standard has been amended and revised successively, on several occasions. The latest version issued in 2008 includes changes on the accounting of interests that do not control and the loss of control on a subsidiary. The actual version also includes the subsequent amendments resulting from IFRS issued until 31st of December 2010. This paper presents the essential aspects of IAS 27 (the actual version and a practical example of how to elaborate consolidated accounts in accordance with this standard.

  9. Consolidation properties of the mudstones from the Harwell boreholes

    International Nuclear Information System (INIS)

    McEwen, T.J.; Hobbs, P.; Horseman, S.T.

    1983-03-01

    Long term high stress consolidation tests have been performed on samples of Oxford Clay, Gault clay, Kimmeridge clay and Lower Lias clay from beneath the Atomic Energy Research Establishment, Harwell, Oxfordshire. In addition to calculating the modulus of volume change and the coefficient of consolidation for each sample, reconstruction of the true one-dimensional consolidation behaviour has been attempted. One dimensional vertical permeabilities have been calculated for samples of Oxford Clay and are compared with those measured by hydraulic testing. Tests were performed in a specially modified oedometer cell using an adapted Denison dead weight loading system in order to produce the required high consolidation stresses. Only one sample, that of Kimmeridge Clay, gave a classical and easily interpretable, consolidation curve, and because of this the OCR (Overconsolidation Ratio) values from other curves have been corrected with respect to this one. This discrepancy between laboratory derived OCRs (OCRLAB) and those calculated from geological information (OCRGEOL) is interesting and is ascribed in this report to apparent overconsolidation caused by secondary compression. Hydraulic conductivities calculated from the oedometer tests at the in situ stresses expected in the Oxford Clay at 273 m depth lie in the range from 4.6 to 5.4 x 10 -12 ms -1 . (author)

  10. Land Mobility in a Central and Eastern European Land Consolidation Context

    DEFF Research Database (Denmark)

    Hartvigsen, Morten B.

    2014-01-01

    in a Central and Eastern European land consolidation context. The term land mobility is defined and the limited theory available is reviewed. Case studies of land mobility in land consolidation pilot projects in Moldova, Albania and Bosnia-Herzegovina show the correlation between land mobility and the success......In most of the Central and Eastern European countries, land reforms after 1989 have resulted in extensive land fragmentation. The majority of the countries have during the two recent decades introduced land consolidation instruments to address the structural problems with land fragmentation...... or failure of voluntary land consolidation projects. In situations with low land mobility, land consolidation instruments need in order to be successful to be supported by other land policy tools such as land banks. The use of existing state agricultural land is an obvious foundation for establishing a state...

  11. Slow oscillations orchestrating fast oscillations and memory consolidation.

    Science.gov (United States)

    Mölle, Matthias; Born, Jan

    2011-01-01

    Slow-wave sleep (SWS) facilitates the consolidation of hippocampus-dependent declarative memory. Based on the standard two-stage memory model, we propose that memory consolidation during SWS represents a process of system consolidation which is orchestrated by the neocortical memory. The slow oscillations temporally group neuronal activity into up-states of strongly enhanced neuronal activity and down-states of neuronal silence. In a feed-forward efferent action, this grouping is induced not only in the neocortex but also in other structures relevant to consolidation, namely the thalamus generating 10-15Hz spindles, and the hippocampus generating sharp wave-ripples, with the latter well known to accompany a replay of newly encoded memories taking place in hippocampal circuitries. The feed-forward synchronizing effect of the slow oscillation enables the formation of spindle-ripple events where ripples and accompanying reactivated hippocampal memory information become nested into the single troughs of spindles. Spindle-ripple events thus enable reactivated memory-related hippocampal information to be fed back to neocortical networks in the excitable slow oscillation up-state where they can induce enduring plastic synaptic changes underlying the effective formation of long-term memories. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Better than sleep: theta neurofeedback training accelerates memory consolidation.

    Science.gov (United States)

    Reiner, Miriam; Rozengurt, Roman; Barnea, Anat

    2014-01-01

    Consistent empirical results showed that both night and day sleep enhanced memory consolidation. In this study we explore processes of consolidation of memory during awake hours. Since theta oscillations have been shown to play a central role in exchange of information, we hypothesized that elevated theta during awake hours will enhance memory consolidation. We used a neurofeedback protocol, to enhance the relative power of theta or beta oscillations. Participants trained on a tapping task, were divided into three groups: neurofeedback theta; neurofeedback beta; control. We found a significant improvement in performance in the theta group, relative to the beta and control groups, immediately after neurofeedback. Performance was further improved after night sleep in all groups, with a significant advantage favoring the theta group. Theta power during training was correlated with the level of improvement, indicating a clear relationship between memory consolidation, and theta neurofeedback. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Local communities’ consolidation process: political factors

    Directory of Open Access Journals (Sweden)

    V. V. Fedorenko

    2017-04-01

    It has been underlined that the local communities’ consolidation process in the contemporary world is the problem which has both empirical and theoretical importance. Depending on the size of the local area, local polices are taking different forms. As usual, they provide an agreement and compromise solutions based on issues that are important to the local community. The experience of the developed democracies has shown that local assemblies ensure the establishment of coalitions based on short-termed procedures. The study has tested that an important aspect of the formation of local communities consolidated position is based on development issues and civil participation. It is especially visible in the United States and the EU countries. The municipality level determines the quality of local political bodies, which is formed on party basis. For contemporary Ukraine important tools for provision of political responsibility are forces, which take care about the local communities and determine their development for a long period. Overall, the consolidation of political forces in the local government system is an important task that determines the need for the adoption of regulatory instruments which would ensure the harmonious and constructive political cooperation regardless of their ideological positions.

  14. Tantalum powder consolidation, modeling and properties

    International Nuclear Information System (INIS)

    Bingert, S.R.; Vargas, V.D.; Sheinberg, H.C.

    1996-01-01

    A systematic approach was taken to investigate the consolidation of tantalum powders. The effects of sinter time, temperature and ramp rate; hot isostatic pressing (HIP) temperature and time; and powder oxygen content on consolidation density, kinetics, microstructure, crystallographic texture, and mechanical properties have been evaluated. In general, higher temperatures and longer hold times resulted in higher density compacts with larger grain sizes for both sintering and HIP'ing. HIP'ed compacts were consistently higher in density than sintered products. The higher oxygen content powders resulted in finer grained, higher density HIP'ed products than the low oxygen powders. Texture analysis showed that the isostatically processed powder products demonstrated a near random texture. This resulted in isotropic properties in the final product. Mechanical testing results showed that the HIP'ed powder products had consistently higher flow stresses than conventionally produced plates, and the sintered compacts were comparable to the plate material. A micromechanics model (Ashby HIP model) has been employed to predict the mechanisms active in the consolidation processes of cold isostatic pressing (CIP), HIP and sintering. This model also predicts the density of the end product and whether grain growth should be expected under the applied processing conditions

  15. Consolidation equipment for irradiated nuclear fuel channels

    International Nuclear Information System (INIS)

    Taguchi, M.; Komatsu, Y.; Ose, T.

    1989-01-01

    The authors have developed and put into use a new type of mechanical consolidation equipment for irradiated nuclear fuel channels. This includes round-slice cutting of the top 100mm of the fuel channel with a guillotine cutter, and press cutting of the two corners of the remaining length of the fuel channel. Four guillotine blades work in combination with receiving blades arranged inside the fuel channel to cut the top 100mm, including the clips and spacers, of the fuel channel into a round slice. A press assembled in the consolidation equipment then presses the slice to achieve volume reduction. The press cutting operation uses two press cutting blades arranged inside the fuel channel and the receiving blades outside the fuel channel. The remaining length of fuel channel is cut off into L-shaped pieces by press cutting. This consolidation equipment is highly efficient because the round-slice cutting, pressing, and press cutting are all achieved by one unit

  16. Retrieval as a Fast Route to Memory Consolidation.

    Science.gov (United States)

    Antony, James W; Ferreira, Catarina S; Norman, Kenneth A; Wimber, Maria

    2017-08-01

    Retrieval-mediated learning is a powerful way to make memories last, but its neurocognitive mechanisms remain unclear. We propose that retrieval acts as a rapid consolidation event, supporting the creation of adaptive hippocampal-neocortical representations via the 'online' reactivation of associative information. We describe parallels between online retrieval and offline consolidation and offer testable predictions for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. How useful is consolidation of public sector entities' financial statements ?

    OpenAIRE

    Soguel, N.; Bucher, R.

    2013-01-01

    Whether or not to consolidate financial statements is dealt with in IPSAS#6. This standard is by and large based on IAS#27. It deals with the criterion according to which an entity's financial statements should be considered and which consolidation technique should be used. However, it remains silent when it comes to exposing the reason why a public sector entity should consolidate its financial statements. The literature is almost as silent as IPSAS on this issue. Which means that there is a...

  18. Ultrasonic assisted consolidation of commingled thermoplastic/glass fibers rovings

    Directory of Open Access Journals (Sweden)

    Francesca eLionetto

    2015-04-01

    Full Text Available Thermoplastic matrix composites are finding new applications in different industrial area thanks to their intrinsic advantages related to environmental compatibility and processability. The approach presented in this work consists in the development of a technology for the simultaneous deposition and consolidation of commingled thermoplastic rovings through to the application of high energy ultrasound. An experimental equipment, integrating both fiber impregnation and ply consolidation in a single process, has been designed and tested. It is made of an ultrasonic welder, whose titanium sonotrode is integrated on a filament winding machine. During winding, the commingled roving is at the same time in contact with the mandrel and the horn. The intermolecular friction generated by ultrasound is able to melt the thermoplastic matrix and impregnate the reinforcement fibers. The heat transfer phenomena occurring during the in situ consolidation were simulated solving by finite element (FE analysis an energy balance accounting for the heat generated by ultrasonic waves and the melting characteristics of the matrix. To this aim, a calorimetric characterization of the thermoplastic matrix has been carried out to obtain the input parameters for the model. The FE analysis has enabled to predict the temperature distribution in the composite during heating and cooling The simulation results have been validated by the measurement of the temperature evolution during ultrasonic consolidation.The reliability of the developed consolidation equipment was proved by producing hoop wound cylinder prototypes using commingled continuous E-glass rovings and Polypropylene (PP filaments. The consolidated composite cylinders are characterized by high mechanical properties, with values comparable with the theoretical ones predicted by the micromechanical analysis.

  19. Review on the explosive consolidation methods to fabricate tungsten based PFMs

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shuming, E-mail: wangshuming@ustb.edu.cn; Sun, Chongxiao; Guo, Wenhao; Yan, Qingzhi; Zhou, Zhangjian; Zhang, Yingchun; Shen, Weiping; Ge, Changchun

    2014-12-15

    Tungsten is one of the best candidates for plasma-facing materials in the fusion reactors, owing to its many unique properties. In the development of tungsten-based Plasma Facing Materials/Components (PFMs/PFCs), materials scientists have explored many different, innovative preparation and processing routes to meet the requirement of International Thermonuclear Experimental Reactor (ITER). Some explosive consolidation technology intrinsic characteristics, which make it suitable for powder metallurgy (powders consolidation) and PFMs production, are the high pressure processing, highly short heating time and can be considered as a highly competitive green technology. In this work, an overview of explosive consolidation techniques applied to fabricate tungsten-based PFMs is presented. Emphasis is given to describe the main characteristics and potentialities of the explosive sintering, explosive consolidation techniques. The aspects presented and discussed in this paper indicate the explosive consolidation processes as a promising and competitive technology for tungsten-based PFMs processing.

  20. Saltmarsh creek bank stability: Biostabilisation and consolidation with depth

    Science.gov (United States)

    Chen, Y.; Thompson, C. E. L.; Collins, M. B.

    2012-03-01

    The stability of cohesive sediments of a saltmarsh in Southern England was measured in the field and the laboratory using a Cohesive Strength Meter (CSM) and a shear vane apparatus. Cores and sediment samples were collected from two tidal creek banks, covered by Atriplex portulacoides (Sea Purslane) and Juncus maritimus (Sea Rush), respectively. The objectives of the study were to examine the variation of sediment stability throughout banks with cantilevers present and investigate the influence of roots and downcore consolidation on bank stability. Data on erosion threshold and shear strength were interpreted with reference to bank depth, sediment properties and biological influences. The higher average erosion threshold was from the Sea Purslane bank whilst the Sea Rush bank showed higher average vane shear strength. The vertical variation in core sediment stability was mainly affected by roots and downcore consolidation with depth. The data obtained from the bank faces revealed that vertical variations in both erosion threshold and vane shear strength were affected primarily by roots and algae. A quantitative estimate of the relative contributions of roots and downcore consolidation to bank sediment stability was undertaken using the bank stability data and sediment density data. This showed that roots contributed more to the Sea Purslane bank stability than downcore consolidation, whilst downcore consolidation has more pronounced effects on the Sea Rush bank stability.

  1. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

    Science.gov (United States)

    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-05-01

    Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

  2. Hospital consolidation outlook: surviving in a tough economy.

    Science.gov (United States)

    Myers, Chris; Lineen, Jason

    2009-11-01

    The rapid hospital consolidation activity of the late 1990s has tapered off, but it's expected to pick up again. The reasons for hospital consolidation have shifted from gaining leverage with payers to achieving cost savings and operating efficiencies to survive in the market. The hospital industry can expect to undergo more profound structural and organizational changes in the decade ahead than it did in the past decade.

  3. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 8 discusses Control System SOT Tests Results and Analysis Report. This is a continuation of Book 7

  4. Centralized consolidation/recycling center

    International Nuclear Information System (INIS)

    St. Georges, L.T.; Poor, A.D.

    1995-05-01

    There are approximately 175 separate locations on the Hanford Site where dangerous waste is accumulated in hundreds of containers according to compatibility. Materials that are designated as waste could be kept from entering the waste stream by establishing collection points for these materials and wastes and then transporting them to a centralized consolidation/recycling center (hereinafter referred to as the consolidation center). Once there the materials would be prepared for offsite recycling. This document discusses the removal of batteries, partially full aerosol cans, and DOP light ballasts from the traditional waste management approach, which eliminates 89 satellite accumulation areas from the Hanford Site (43 for batteries, 33 for aerosols, and 13 for DOP ballasts). Eliminating these 89 satellite accumulation areas would reduce by hundreds the total number of containers shipped offsite as hazardous waste (due to the increase in containers when the wastes that are accumulated are segregated according to compatibility for final shipment). This new approach is in line with the U.S. Environmental Protection Agency's (EPA) draft Universal Waste Rules for these open-quotes nuisanceclose quotes and common waste streams. Additionally, future reviews of other types of wastes that can be handled in this less restrictive and more cost-effective manner will occur as part of daily operations at the consolidation center. The Hanford Site has been identified as a laboratory for reinventing government by the Secretary of the U.S. Department of Energy (DOE), Hazel O'Leary, and as a demonstration zone where open-quotes innovative ideas, processes and technologies can be created, tested and demonstrated.close quotes Additionally, DOE, EPA, and the Washington State Department of Ecology (Ecology) have agreed to cut Hanford cleanup costs by $1 billion over a 5-year period

  5. Sleep-dependent memory consolidation--what can be learnt from children?

    Science.gov (United States)

    Wilhelm, I; Prehn-Kristensen, A; Born, J

    2012-08-01

    Extensive research has been accumulated demonstrating that sleep is essential for processes of memory consolidation in adults. In children and infants, a great capacity to learn and to memorize coincides with longer and more intense sleep. Here, we review the available data on the influence of sleep on memory consolidation in healthy children and infants, as well as in children with attention-deficit/hyperactivity disorder (ADHD) as a model of prefrontal impairment, and consider possible mechanisms underlying age-dependent differences. Findings indicate a major role of slow wave sleep (SWS) for processes of memory consolidation during early development. Importantly, longer and deeper SWS during childhood appears to produce a distinctly superior strengthening of hippocampus-dependent declarative memories, but concurrently prevents an immediate benefit from sleep for procedural memories, as typically observed in adults. Studies of ADHD children point toward an essential contribution of prefrontal cortex to the preferential consolidation of declarative memory during SWS. Developmental studies of sleep represent a particularly promising approach for characterizing the supra-ordinate control of memory consolidation during sleep by prefrontal-hippocampal circuitry underlying the encoding of declarative memory. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Consolidation of nanometer-sized aluminum single crystals: Microstructure and defects evolutions

    KAUST Repository

    Afify, N. D.

    2014-04-01

    Deriving bulk materials with ultra-high mechanical strength from nanometer-sized single metalic crystals depends on the consolidation procedure. We present an accurate molecular dynamics study to quantify microstructure responses to consolidation. Aluminum single crystals with an average size up to 10.7 nm were hydrostatically compressed at temperatures up to 900 K and pressures up to 5 GPa. The consolidated material developed an average grain size that grew exponentially with the consolidation temperature, with a growth rate dependent on the starting average grain size and the consolidation pressure. The evolution of the microstructure was accompanied by a significant reduction in the concentration of defects. The ratio of vacancies to dislocation cores decreased with the average grain size and then increased after reaching a critical average grain size. The deformation mechanisms of poly-crystalline metals can be better understood in the light of the current findings. © 2013 Elsevier B.V. All rights reserved.

  7. Consolidation of nanometer-sized aluminum single crystals: Microstructure and defects evolutions

    KAUST Repository

    Afify, N. D.; Salem, H. G.; Yavari, A.; El Sayed, Tamer S.

    2014-01-01

    Deriving bulk materials with ultra-high mechanical strength from nanometer-sized single metalic crystals depends on the consolidation procedure. We present an accurate molecular dynamics study to quantify microstructure responses to consolidation. Aluminum single crystals with an average size up to 10.7 nm were hydrostatically compressed at temperatures up to 900 K and pressures up to 5 GPa. The consolidated material developed an average grain size that grew exponentially with the consolidation temperature, with a growth rate dependent on the starting average grain size and the consolidation pressure. The evolution of the microstructure was accompanied by a significant reduction in the concentration of defects. The ratio of vacancies to dislocation cores decreased with the average grain size and then increased after reaching a critical average grain size. The deformation mechanisms of poly-crystalline metals can be better understood in the light of the current findings. © 2013 Elsevier B.V. All rights reserved.

  8. Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation.

    Science.gov (United States)

    Wang, Dong V; Yau, Hau-Jie; Broker, Carl J; Tsou, Jen-Hui; Bonci, Antonello; Ikemoto, Satoshi

    2015-05-01

    Sharp wave-associated field oscillations (∼200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity. Notably, using a fear conditioning procedure, we found that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation.

  9. Post-learning molecular reactivation underlies taste memory consolidation

    Directory of Open Access Journals (Sweden)

    Kioko eGuzman-Ramos

    2011-09-01

    Full Text Available It is considered that memory consolidation is a progressive process that requires post-trial stabilization of the information. In this regard, it has been speculated that waves of receptors activation, expression of immediate early genes and replenishment of receptor subunit pools occur to induce functional or morphological changes to maintain the information for longer periods. In this paper, we will review data related to neuronal changes in the post-acquisition stage of taste aversion learning that could be involved in further stabilization of the memory trace. In order to achieve such stabilization, evidence suggests that the functional integrity of the insular cortex (IC and the amygdala (AMY is required. Particularly the increase of extracellular levels of glutamate and activation of N-methyl-D-aspartate (NMDA receptors within the IC shows a main role in the consolidation process. Additionally the modulatory actions of the dopaminergic system in the IC appear to be involved in the mechanisms that lead to taste aversion memory consolidation through the activation of pathways related to enhancement of protein synthesis such as the Protein Kinase A pathway. In summary, we suggest that post-acquisition molecular and neuronal changes underlying memory consolidation are dependent on the interactions between the AMY and the IC.

  10. The Limited Capacity of Sleep-Dependent Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Gordon B Feld

    2016-09-01

    Full Text Available Sleep supports memory consolidation. However, the conceptually important influence of the amount of items encoded in a memory test on this effect has not been investigated. In two experiments, participants (n=101 learned lists of word-pairs varying in length (40, 160, 320 word-pairs in the evening before a night of sleep (sleep group or of sleep deprivation (wake group. After 36 h (including a night allowing recovery sleep retrieval was tested. Compared with wakefulness, post-learning sleep enhanced retention for the 160 word-pair condition (p < 0.01, importantly, this effect completely vanished for the 320 word-pair condition. This result indicates a limited capacity for sleep-dependent memory consolidation, which is consistent with an active system consolidation view on sleep’s role for memory, if it is complemented by processes of active forgetting and/or gist abstraction. Whereas the absolute benefit from sleep should have increased with increasing amounts of successfully encoded items, if sleep only passively protected memory from interference. Moreover, the finding that retention performance was significantly diminished for the 320 word-pair condition compared to the 160 word-pair condition in the sleep group, makes it tempting to speculate that with increasing loads of information encoded during wakefulness, sleep might favour processes of forgetting over consolidation.

  11. Consolidation by Prefabricated Vertical Drains with a Threshold Gradient

    Directory of Open Access Journals (Sweden)

    Xiao Guo

    2014-01-01

    Full Text Available This paper shows the development of an approximate analytical solution of radial consolidation by prefabricated vertical drains with a threshold gradient. To understand the effect of the threshold gradient on consolidation, a parametric analysis was performed using the present solution. The applicability of the present solution was demonstrated in two cases, wherein the comparisons with Hansbo’s results and observed data were conducted. It was found that (1 the flow with the threshold gradient would not occur instantaneously throughout the whole unit cell. Rather, it gradually occurs from the vertical drain to the outside; (2 the moving boundary would never reach the outer radius of influence if R+1consolidation; (4 the larger the threshold gradient is, the greater the long-term excess pore pressure will be; and (5 the present solution could predict the consolidation behavior in soft clay better than previous methods.

  12. The role of the ventromedial prefrontal cortex in memory consolidation

    NARCIS (Netherlands)

    Nieuwenhuis, I.L.C.; Takashima, A.

    2011-01-01

    System-level memory consolidation theory posits that the hippocampus initially links the neocortical representations, followed by a shift to a hippocampus-independent neocortical network. With consolidation, an increase in activity in the human subgenual ventromedial prefrontal cortex (vmPFC) has

  13. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  14. A thermomechanical crystal plasticity constitutive model for ultrasonic consolidation

    KAUST Repository

    Siddiq, Amir

    2012-01-01

    We present a micromechanics-based thermomechanical constitutive model to simulate the ultrasonic consolidation process. Model parameters are calibrated using an inverse modeling approach. A comparison of the simulated response and experimental results for uniaxial tests validate and verify the appropriateness of the proposed model. Moreover, simulation results of polycrystalline aluminum using the identified crystal plasticity based material parameters are compared qualitatively with the electron back scattering diffraction (EBSD) results reported in the literature. The validated constitutive model is then used to simulate the ultrasonic consolidation process at sub-micron scale where an effort is exerted to quantify the underlying micromechanisms involved during the ultrasonic consolidation process. © 2011 Elsevier B.V. All rights reserved.

  15. A consolidation process for spent burnable poison rod assemblies

    International Nuclear Information System (INIS)

    Yamamoto, Y.; Harada, M.; Komatsu, Y.

    1985-01-01

    A new consolidation system for the spent burnable poison assembly utilizing a sequence control robot operated under water was proposed. A credible accident in the system was analyzed mainly from the viewpoint of tritium release, based on the diffusion analysis of tritium in borosilicate glass. It was found that the amount of tritium released would be small even after the rupture of burnable poison rods. An experiment on a new consolidation system was performed using spent burnable poison assemblies. The volume of burnable poison assemblies was reduced safely and securely by a factor of 7 to 14 for burnable poison rods and by 22 for hold-down portions. It was proved that the consolidation system is collectively feasible

  16. Consolidation in World Steel Industry - Implications for Poland

    OpenAIRE

    Beata Ślusarczyk

    2009-01-01

    Consolidation of enterprises has intensified with the growth of global competition. In the nineties of the past century, these processes became a conventional way for market expansion, leading to establishment of huge international companies with biggest influence on world economy. In steel industry, processes of consolidation have also been the leading processes in management, particularly during a time of prosperity for steel products that have taken place in recent years. The global consol...

  17. Deconsolidation and combustion performance of thermally consolidated propellants deterred by multi-layers coating

    Directory of Open Access Journals (Sweden)

    Zheng-gang Xiao

    2014-06-01

    Full Text Available Both heating and solvent-spray methods are used to consolidate the standard grains of double-base oblate sphere propellants plasticized with triethyleneglycol dinitrate (TEGDN (TEGDN propellants to high density propellants. The obtained consolidated propellants are deterred and coated with the slow burning multi-layer coating. The maximum compaction density of deterred and coated consolidated propellants can reach up to 1.39 g/cm3. Their mechanic, deconsolidation and combustion performances are tested by the materials test machine, interrupted burning set-up and closed vessel, respectively. The static compression strength of consolidated propellants deterred by multi-layer coating increases significantly to 18 MPa, indicating that they can be applied in most circumstances of charge service. And the samples are easy to deconsolidate in the interrupted burning test. Furthermore, the closed bomb burning curves of the samples indicate a two-stage combustion phenomenon under the condition of certain thickness of coated multi-layers. After the outer deterred multi-layer coating of consolidated samples is finished burning, the inner consolidated propellants continue to burn and breakup into aggregates and grains. The high burning progressivity can be carefully obtained by the smart control of deconsolidation process and duration of consolidated propellants. The preliminary results of consolidated propellants show that a rapid deconsolidation process at higher deconsolidation pressure is presented in the dynamic vivacity curves of closed bomb test. Higher density and higher macro progressivity of consolidated propellants can be obtained by the techniques in this paper.

  18. [Activating effect of adrenaline, prednisolone and vincristine in the late periods of tick-borne encephalitis virus persistence].

    Science.gov (United States)

    Frolova, T V; Pogodina, V V

    1984-01-01

    The activating effect of adrenalin (A), prednisolone (P), and vincristine (V) on persistent infection caused by subcutaneous inoculation of Syrian hamsters with the Vasilchenko and B-383 strains of tick-borne encephalitis virus (TBE) was studied. The drugs were administered once, twice, or three times 250-270 days after virus inoculation. Complement-fixing antigen was found in the organs of the infected animals given no A, P, or V; in the organ explants synthesis of hemagglutinin was observed but no infectious virus could be isolated. After treatment of the infected hamsters with A, P, or V organ explants yielded TBE virus strains which showed either high or low virulence for white mice. The activated TBE virus strains were obtained from explants of hamster brains and spleens but not liver. V produced the most marked activating effect, A the least.

  19. Student Loans Driving You Crazy? A Borrower's Guide to Direct Consolidation Loans.

    Science.gov (United States)

    Office of Federal Student Aid (ED), Washington, DC.

    This booklet describes the Direct Consolidation Loan program students can use to combine one or more student loans into a new loan. Things to consider before seeking a consolidation loan are outlined. Direct consolidation loans offer a number of advantages; they are free, result in one lender and one monthly payment, and offer flexible repayment…

  20. 17 CFR 230.145 - Reclassification of securities, mergers, consolidations and acquisitions of assets.

    Science.gov (United States)

    2010-04-01

    ..., mergers, consolidations and acquisitions of assets. 230.145 Section 230.145 Commodity and Securities... § 230.145 Reclassification of securities, mergers, consolidations and acquisitions of assets.... A statutory merger or consolidation or similar plan or acquisition in which securities of such...

  1. CONSOLIDATED FINANCIAL STATEMENTS IN UKRAINE: NORMATIVE AND LEGAL REGULATION STATE

    Directory of Open Access Journals (Sweden)

    S.V. Kucher

    2016-09-01

    Full Text Available The development of big business in Ukraine has led to the need to release a number of domestic companies and their groups and associations to the international financial market which was the prerequisite of the needs of users of financial statements to obtain reliable information about the activities of such companies. In accordance with the national legislation associations of enterprises and companies have to provide the consolidated financial statements which contain the pooled indices about the activities of these entities. The article analyzes the current state of normative and legal regulation of financial reporting consolidation process in Ukraine. In particular, the paper determines the basic legal acts of regulations of national and international governing process of preparation of consolidated financial statements; it also determines the circle of business entities required to draw up the consolidated financial statements solely in accordance with international financial reporting standards.

  2. Consolidation of W–Ta composites: Hot isostatic pressing and spark and pulse plasma sintering

    Energy Technology Data Exchange (ETDEWEB)

    Dias, M., E-mail: marta.dias@itn.pt [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Guerreiro, F. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Correia, J.B. [LNEG, Laboratório Nacional de Energia e Geologia, Estrada do Paço do Lumiar, 1649-038 Lisboa (Portugal); Galatanu, A. [National Institute of Materials Physics, Atomistilor 105 bis Bucharest-Magurele, 077125 Ilfov (Romania); Rosiński, M. [Warsaw University of Technology, Faculty of Materials Science and Engineering, Warsaw (Poland); Monge, M.A.; Munoz, A. [Departamento de Física, Univerdidad Carlos III de Madrid, Avd. de la Universidad 30, 28911 Madrid (Spain); Alves, E. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Carvalho, P.A. [Instituto de Plasmas e Fusão Nuclear, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal); CeFEMA, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa (Portugal)

    2015-10-15

    Highlights: • Consolidation of W–Ta composites using three techniques: HIP, SPS and PPS. • Comparison of consolidation methods in terms of W–Ta interdiffusion and densification. • Microstructure analysis in terms of oxides formation. - Abstract: Composites consisting of tantalum fiber/powder dispersed in a nanostructured W matrix have been consolidated by spark and pulse plasma sintering as well as by hot isostatic pressing. The microstructural observations revealed that the tungsten–tantalum fiber composites consolidated by hot isostatic pressing and pulse plasma sintering presented a continuous layer of Ta{sub 2}O{sub 5} phase at the W/Ta interfaces, while the samples consolidated by spark plasma sintering evidenced a Ta + Ta{sub 2}O{sub 5} eutectic mixture due to the higher temperature of this consolidation process. Similar results have been obtained for the tungsten–tantalum powder composites. A (W, Ta) solid solution was detected around the prior nanostructured W particles in tungsten–tantalum powder composites consolidated by spark and pulse plasma sintering. Higher densifications were obtained for composites consolidated by hot isostatic pressing and pulse plasma sintering.

  3. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 2 discusses the following topics: Fuel Rod Extraction System Test Results and Analysis Reports and Clamping Table Test Results and Analysis Reports

  4. The role of sleep in declarative memory consolidation--direct evidence by intracranial EEG.

    NARCIS (Netherlands)

    Axmacher, N.; Haupt, S.; Fernandez, G.S.E.; Elger, C.E.; Fell, J.

    2008-01-01

    Two step theories of memory formation assume that an initial learning phase is followed by a consolidation stage. Memory consolidation has been suggested to occur predominantly during sleep. Very recent findings, however, suggest that important steps in memory consolidation occur also during waking

  5. High-energy, high-rate consolidation of tungsten and tungsten-based composite powders

    Energy Technology Data Exchange (ETDEWEB)

    Raghunathan, S.K.; Persad, C.; Bourell, D.L.; Marcus, H.L. (Center for Materials Science and Engineering, Univ. of Texas, Austin (USA))

    1991-01-20

    Tungsten and tungsten-based heavy alloys are well known for their superior mechanical properties at elevated temperatures. However, unalloyed tungsten is difficult to consolidate owing to its very high melting temperature (3683 K). The additions of small amounts of low-melting elements such as iron, nickel, cobalt and copper, facilitate the powder processing of dense heavy alloys at moderate temperatures. Energetic high-current pulses have been used recently for powder consolidation. In this paper, the use of a homopolar generator as a power source to consolidate selected tungsten and tungsten-based alloys is examined. Various materials were consolidated including unalloyed tungsten, W-Nb, W-Ni, and tungsten heavy alloy with boron carbide. The effect of process parameters such as pressure and specific energy input on the consolidation of different alloy systems is described in terms of microstructure and property relationships. (orig.).

  6. PROBLEM ASPECTS OF FORMATION OF THE LEGAL INSTITUTE OF CONSOLIDATED TAXPAYERS’ GROUPS IN RUSSIA

    Directory of Open Access Journals (Sweden)

    Irina Glazunova

    2017-01-01

    Full Text Available The subject. The article is devoted to the prerequisites of the emergence and essential characteristics of the institution of consolidated taxpayers’ groups in Russia and abroad, revealing of advantages and disadvantages of the legal regulation of the creation and operation of consolidated groups of payers of corporate profits tax, analyzing results and directions of the development of tax consolidation in Russian Federation.The purpose of the article is to identify positive and negative aspects of the functioning of the institution of consolidated taxpayers’ groups in Russia with the establishment of prospects of tax consolidation and the likely directions of its development.The description of the problem field. The development of the world economic system stimulates the emergence of new forms of management, characterized by the enlargement of busi-ness, the pooling of resources of individual enterprises into a single system in order to optimize entrepreneurial activity. These trends are reflected in the development of tax systems of various countries, that is expressed in the formation of institutions of consolidated taxpayers’ groups. Tax consolidation in Russia is a relatively new phenomenon, and it seems necessary to examine this institution from the law enforcement point of view, to evaluate its effectiveness.Methods and methodology. The authors used methods of analysis, synthesis, as well as formal-legal, comparative-legal, historical methods of investigation.Results and the scope of its application. The authors note that the institution of tax consolidation today is presented in the tax systems of most modern countries.The practice of applying the institution of consolidated taxpayers’ groups testifies to the existence of a significant number of advantages and disadvantages of tax consolidation in Russia. The moratorium on the creation of consolidated taxpayers’ groups, due to the contradictory nature of their influence on the

  7. 75 FR 51158 - BDB Company-Acquisition Exemption-Consolidated Rail Corporation

    Science.gov (United States)

    2010-08-18

    ... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35398] BDB Company--Acquisition Exemption--Consolidated Rail Corporation BDB Company (BDB), a noncarrier, has filed a verified notice of exemption under 49 CFR 1150.31 to acquire from Consolidated Rail Corporation a parcel of land...

  8. Consolidation modelling for thermoplastic composites forming simulation

    Science.gov (United States)

    Xiong, H.; Rusanov, A.; Hamila, N.; Boisse, P.

    2016-10-01

    Pre-impregnated thermoplastic composites are widely used in the aerospace industry for their excellent mechanical properties, Thermoforming thermoplastic prepregs is a fast manufacturing process, the automotive industry has shown increasing interest in this manufacturing processes, in which the reconsolidation is an essential stage. The model of intimate contact is investigated as the consolidation model, compression experiments have been launched to identify the material parameters, several numerical tests show the influents of the temperature and pressure applied during processing. Finally, a new solid-shell prismatic element has been presented for the simulation of consolidation step in the thermoplastic composites forming process.

  9. Review and evaluation of metallic TRU nuclear waste consolidation methods

    International Nuclear Information System (INIS)

    Montgomery, D.R.; Nesbitt, J.F.

    1983-08-01

    The US Department of Energy established the Commercial Waste Treatment Program to develop, demonstrate, and deploy waste treatment technology. In this report, viable methods are identified that could consolidate the volume of metallic wastes generated in a fuel reprocessing facility. The purpose of this study is to identify, evaluate, and rate processes that have been or could be used to reduce the volume of contaminated/irradiated metallic waste streams and to produce an acceptable waste form in a safe and cost-effective process. A technical comparative evaluation of various consolidation processes was conducted, and these processes were rated as to the feasibility and cost of producing a viable product from a remotely operated radioactive process facility. Out of the wide variety of melting concepts and consolidation systems that might be applicable for consolidating metallic nuclear wastes, the following processes were selected for evaluation: inductoslay melting, rotating nonconsumable electrode melting, plasma arc melting, electroslag melting with two nonconsumable electrodes, vacuum coreless induction melting, and cold compaction. Each process was evaluated and rated on the criteria of complexity of process, state and type of development required, safety, process requirements, and facility requirements. It was concluded that the vacuum coreless induction melting process is the most viable process to consolidate nuclear metallic wastes. 11 references

  10. Consolidated Audit And Compliance System (CACS)

    Data.gov (United States)

    US Agency for International Development — Consolidated Audit and Compliance System: is an audit findings management and reporting system. CACS is an implementation of the Agency Secure Image and Storage...

  11. Nuclear weapons complex. Weaknesses in DOE's nonnuclear consolidation plan

    International Nuclear Information System (INIS)

    Wells, James E. Jr.; Fenzel, William F.; Schulze, John R.; Gaffigan, Mark E.

    1992-11-01

    Nuclear weapons contain a wide variety of nonnuclear components - items that are not made from nuclear materials. These components comprise the majority of parts in nuclear weapons, including the ones needed to guide weapons to their targets, initiate the nuclear explosion, increase the weapons' explosive yield, and ensure the weapons' safety and security. DOE has three facilities, the Kansas City Plant in Missouri, the Mound Plant in Ohio, and the Pinellas Plant in Florida, that are dedicated primarily to nonnuclear activities and have unique manufacturing responsibilities. Some additional nonnuclear manufacturing activities are performed at the Rocky Flats Plant in Colorado, the Y-12 Plant in Tennessee, and the Pantex Plant in Texas. Descriptions of each plant and the activities they conduct are contained in appendix I of this report. In 1991, DOE began planning to reconfigure the nuclear weapons complex into one that is smaller, less diverse, and less expensive to operate. More specifically, DOE issued a reconfiguration study in January 1991 that set forth a detailed framework for making the complex smaller and more efficient. The study will lead to a complex-wide Programmatic Environmental Impact Statement (PEIS) on how best to reconfigure the complex. This statement is planned to be completed in late 1993. As part of the effort to analyze the reconfiguration, DOE's Assistant Secretary for Defense Programs directed the Albuquerque Operations Office in April 1991 to develop a nonnuclear consolidation plan to serve as input to the PEIS. There are a number of weaknesses in DOE's NCP. First, because the NCP's scope was limited to examining single-site consolidation alternatives, the decision to select Kansas City as the preferred option was made without analyzing other nonnuclear options. These options included down sizing and modernizing all facilities in place or maximizing consolidation by eliminating all nonnuclear sites and relocating their functions to a

  12. Modifying the consolidation depth of nanolime on Maastricht limestone

    Czech Academy of Sciences Publication Activity Database

    Niedoba, Krzysztof; Slížková, Zuzana; Frankeová, Dita; Nunes, Cristiana Lara; Jandejsek, Ivan

    2017-01-01

    Roč. 133, February (2017), s. 51-56 ISSN 0950-0618 R&D Projects: GA MŠk(CZ) LO1219 Keywords : stone consolidation * calcium hydroxide nanoparticles * CaLoSiL * X-ray radiography * drilling resistance * consolidant distribution Subject RIV: AL - Art, Architecture, Cultural Heritage OBOR OECD: Materials engineering Impact factor: 3.169, year: 2016 http://www.sciencedirect.com/science/article/pii/S0950061816317664

  13. CONSIDERAŢII PRIVIND GRUPURILE DE SOCIETĂŢI ŞI SITUAŢIILE FINANCIARE CONSOLIDATE

    Directory of Open Access Journals (Sweden)

    Ştefea Petru

    2011-01-01

    Full Text Available The paper presents some general considerations concerning the groups of companies andannual consolidated financial statements. We tried to deal with the concept of group and theconcept of consolidated financial statements. We presented the consolidated financialsettlements at the international and national level, the utility and the objectives of theconsolidated financial statements and finally the advantages and disadvantages of creating agroup and of elaborating the consolidated financial statements. Creating groups is anecessity and also a reality of contemporary economic life. The consolidated financialstatements are useful to all users, from shareholders to employees.

  14. Prototypical Consolidation Demonstration Project: Final report

    International Nuclear Information System (INIS)

    Gili, J.A.; Poston, V.K.

    1993-11-01

    This is the final report of the Prototypical Consolidation Demonstration Project, which was funded by the US Department of Energy's Office of Civilian Radioactive Waste Management. The project had two objectives: (a) to develop and demonstrate a prototype of production-scale equipment for the dry, horizontal consolidation and packaging of spent nuclear fuel rods from commercial boiling water reactor and pressurized water reactor fuel assemblies, and (b) to report the development and demonstration results to the US Department of Energy, Idaho Operations Office. This report summarizes the activities and conclusions of the project management contractor, EG ampersand G Idaho, Inc., and the fabrication and testing contractor, NUS Corporation (NUS). The report also presents EG ampersand G Idaho's assessments of the equipment and procedures developed by NUS

  15. Consolidation Process for FY 1997 Financial Statements for Other Defense Organizations

    National Research Council Canada - National Science Library

    1998-01-01

    ... to prepare consolidated financial statements for FY 1996 and each succeeding year. The DoD Consolidated Financial Statements for FY 1997 include financial statements for a reporting entity entitled "Other Defense Organizations...

  16. Consolidating the effects of waking and sleep on motor-sequence learning.

    Science.gov (United States)

    Brawn, Timothy P; Fenn, Kimberly M; Nusbaum, Howard C; Margoliash, Daniel

    2010-10-20

    Sleep is widely believed to play a critical role in memory consolidation. Sleep-dependent consolidation has been studied extensively in humans using an explicit motor-sequence learning paradigm. In this task, performance has been reported to remain stable across wakefulness and improve significantly after sleep, making motor-sequence learning the definitive example of sleep-dependent enhancement. Recent work, however, has shown that enhancement disappears when the task is modified to reduce task-related inhibition that develops over a training session, thus questioning whether sleep actively consolidates motor learning. Here we use the same motor-sequence task to demonstrate sleep-dependent consolidation for motor-sequence learning and explain the discrepancies in results across studies. We show that when training begins in the morning, motor-sequence performance deteriorates across wakefulness and recovers after sleep, whereas performance remains stable across both sleep and subsequent waking with evening training. This pattern of results challenges an influential model of memory consolidation defined by a time-dependent stabilization phase and a sleep-dependent enhancement phase. Moreover, the present results support a new account of the behavioral effects of waking and sleep on explicit motor-sequence learning that is consistent across a wide range of tasks. These observations indicate that current theories of memory consolidation that have been formulated to explain sleep-dependent performance enhancements are insufficient to explain the range of behavioral changes associated with sleep.

  17. 49 CFR 172.404 - Labels for mixed and consolidated packaging.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Labels for mixed and consolidated packaging. 172..., TRAINING REQUIREMENTS, AND SECURITY PLANS Labeling § 172.404 Labels for mixed and consolidated packaging. (a) Mixed packaging. When hazardous materials having different hazard classes are packed within the...

  18. Alternate Energy Sources for Thermalplastic Binding Agent Consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Frame, B.J.

    1999-01-01

    A study was conducted to investigate microwave and electron beam technologies as alternate energy sources to consolidate fiber coated with a thermoplastic binding agent into preforms for composite molding applications. Bench experiments showed that both microwave and electron beam energy can produce heat sufficient to melt and consolidate a thermoplastic binding agent applied to fiberglass mat, and several two- and three-dimensional fiberglass preforms were produced with each method. In both cases, it is postulated that the heating was accomplished by the effective interaction of the microwave or electron beam energy with the combination of the mat preform and the tooling used to shape the preform. Both methods contrast with conventional thermal energy applied via infrared heaters or from a heated tool in which the heat to melt the thermoplastic binding agent must diffuse over time from the outer surface of the preform toward its center under a thermal gradient. For these reasons, the microwave and electron beam energy techniques have the potential to rapidly consolidate thick fiber preforms more efficiently than the thermal process. With further development, both technologies have the potential to make preform production more cost effective by decreasing cycle time in the preform tool, reducing energy costs, and by enabling the use of less expensive tooling materials. Descriptions of the microwave and electron beam consolidation experiments and a summary of the results are presented in this report.

  19. Prolonged Suppression of Neuropathic Pain by Sequential Delivery of Lidocaine and Thalidomide Drugs Using PEGylated Graphene Oxide.

    Science.gov (United States)

    Song, Tieying; Gu, Kunfeng; Wang, Wenli; Wang, Hong; Yang, Yunliang; Yang, Lijun; Ma, Pengxu; Ma, Xiaojing; Zhao, Jianhui; Yan, Ruyu; Guan, Jiao; Wang, Chunping; Qi, Yan; Ya, Jian

    2015-11-01

    The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide (GO) bearing two commonly used drugs of lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Definition and Classification of the Stakeholders in Land Consolidation Project

    Institute of Scientific and Technical Information of China (English)

    LIU Xiang-dong; GUO Bi-jun; GUO Mao-xuan

    2012-01-01

    Using the methods of questionnaire survey, statistical analysis and multidimensional rating, we define and classify the stakeholders in land consolidation project. 25 kinds of stakeholders are determined, divided into three categories: core stakeholders, including county-level government, county-level land departments, county-level land consolidation center, the rural collective economic organizations, farmers, township government, and the villagers’ committee; middle stakeholders, including central government, the Ministry of Land and Resources, the Ministry of Land and Resources Land Consolidation Center, the provincial land departments, the provincial land consolidation center, the county-level finance departments, the county-level water resources departments, the government supervisory departments, government audit departments, and the public; peripheral stakeholders, including the county-level environmental protection departments, the county-level agricultural departments, supervisory agencies, design agencies, project contractors, equipment suppliers, material suppliers, and the bidding agencies. The project managers should pay attention to the interest appeal of the stakeholders, and adopt different coping strategies.

  1. Fiscal Consolidation Start and its Determinants Analysis Within European Member Countries

    Directory of Open Access Journals (Sweden)

    Lucia Mihóková

    2017-09-01

    Full Text Available Purpose: The purpose of the research from the theoretical point of view is to define the "start of fiscal consolidation" and to clarify the effects of selected determinants on its initiation. The purpose of the paper, in an empirical context, is to empirically assess the impact of selected determinants on the start of consolidation in the EU member states in 1995-2015 using quantitative economics. The paper was developed within the project VEGA 1/0967/15. Methodology: The empirical assessment of the research objective is divided into four phases: (1 creation of research review using EBHC methodology, (2 identification of “start” of fiscal consolidation within selected period, (3 panel econometric analysis: model specification, quantification of model’s parameters and model verification and (4 research assessment and discussion. Within the analysis, the traditional, specific and general methods were used (systemic review according to EBHC methodology, content analysis, panel regression analysis, synthesis. Approach: Approach identifies “start” of consolidation episodes using selected identification rules. Using the panel regression analysis (OLS, FEM and REM models approach the statistically significant macroeconomic, fiscal, political and other determinants and quantification of the polarity of their impact on the fiscal consolidation start were analysed. Findings: Based on the performed econometric analysis can be stated that the start of consolidation is significantly determined by initial macroeconomic and fiscal situation in the country which are captured by the size of output gap and GDP growth as well as the size of CAPB, budget expenditure and the revenue side. Political and other determinants (such as crisis can also influence the start of consolidation episodes..

  2. 17 CFR 210.3A-02 - Consolidated financial statements of the registrant and its subsidiaries.

    Science.gov (United States)

    2010-04-01

    ... 1975 Consolidated and Combined Financial Statements § 210.3A-02 Consolidated financial statements of... consolidated financial statements principles of inclusion or exclusion which will clearly exhibit the financial... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Consolidated financial...

  3. 17 CFR 210.3A-03 - Statement as to principles of consolidation or combination followed.

    Science.gov (United States)

    2010-04-01

    ... Consolidated and Combined Financial Statements § 210.3A-03 Statement as to principles of consolidation or... of (1) subsidiaries in consolidated or combined financial statements and (2) companies in consolidated or combined financial statements, shall be stated in the notes to the respective financial...

  4. NMR study of nanophase Al/Al-oxide powder and consolidated composites

    International Nuclear Information System (INIS)

    Suits, B.H.; Apte, P.; Wilken, D.E.; Siegel, R.W.

    1994-10-01

    27 Al Nuclear Magnetic Resonance (NMR) measurements from aluminum powders and consolidated nanophase aluminum made from those powders are presented. The signals from the metal and surface oxidation are easily separated and are compared before and after consolidation. The results presented indicate that the oxide coating becomes the interface region within the nanophase composite material and that during consolidation the metal has undergone a deformation equivalent to that seen for bulk material under a compressive strain of between 4% and 8%

  5. CONSOLIDATION POLICY: PAST, PRESENT AND FUTURE APPROACHES TO THE CONCEPT OF CONTROL

    Directory of Open Access Journals (Sweden)

    Ienciu Alin Ionel

    2010-07-01

    Full Text Available Preparing consolidated financial statements has been a common practice for groups of companies around the world for a relatively long time, going back one century in the USA and tens of years in different European countries.A far-reaching issue regarding consolidation accounting policy is the concept of control, as it holds a crucial role in determining the basis of consolidation and the applicable method of consolidation and subsequently in influencing the content of the group financial statements. We focus in our article on the concept of exclusive control as it is approached by the relevant International, American and European standards, casting light also on possible future developments of this concept. The objective of our study is to acknowledge the differences and similarities between the approaches to the control concept, closing with the presentation of the influences of these approaches on the basis of consolidation.

  6. Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

    Science.gov (United States)

    Plihal, W; Born, J

    1999-09-09

    Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

  7. Therapeutic advancements in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Alessandro eGozzetti

    2014-09-01

    Full Text Available Multiple myeloma survival has significantly improved in latest years, due to a broad spectrum of novel agents available for treatment. The introduction of thalidomide, bortezomib and lenalidomide together with autologous stem cell transplantation has dramatically prolonged complete remissions rate, progression free survivals resulting ultimately in prolonged survivals in myeloma patients. Moreover, novel strategies of treatment such as consolidation and maintenance are being used to implement responses. A number of new drugs such as carfilzomib and pomalidomide are already in clinical practice, and new kids on the block are entering, making the future of myeloma patients brighter.

  8. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 9 discusses the following topics: Integrated System Normal Operations Test Results and Analysis Report; Integrated System Off-Normal Operations Test Results and Analysis Report; and Integrated System Maintenance Operations Test Results and Analysis Report

  9. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 1 discusses the following topics: the background of the project; test program description; summary of tests and test results; problem evaluation; functional requirements confirmation; recommendations; and completed test documentation for tests performed in Phase 3

  10. Rod consolidation at the West Valley Demonstration Project

    International Nuclear Information System (INIS)

    Bailey, W.J.

    1986-12-01

    A rod consolidation demonstration with irradiated pressurized water reactor fuel was recently conducted by personnel from Nuclear Assurance Corporation and West Valley Nuclear Services Company at the West Valley Demonstration Project in West Valley, New York. The rod consolidation demonstration involved pulling all of the fuel rods from six fuel Assemblies. In general, the rod pulling proceeded smoothly. The highest compaction ratio attained was 1:8:1. Among the total of 1074 fuel rods were some known degraded rods (they had collapsed cladding, a result of in-reactor fuel densification), but no rods were broken or dropped during the demonstration. One aim was to gather information on the effect of rod consolidation operations on the integrity of the fuel rods during subsequent handling and storage. Another goal was to collect information on the condition and handling of intact, damaged, and failed fuel that has been in storage for an extended period. 9 refs., 8 figs., 1 tab

  11. Susceptibility of memory consolidation during lapses in recall

    Science.gov (United States)

    Marra, Vincenzo; O’Shea, Michael; Benjamin, Paul R.; Kemenes, Ildikó

    2013-01-01

    Memories that can be recalled several hours after learning may paradoxically become inaccessible for brief periods after their formation. This raises major questions about the function of these early memory lapses in the structure of memory consolidation. These questions are difficult to investigate because of the lack of information on the precise timing of lapses. However, the use of a single-trial conditioning paradigm in Lymnaea solves this problem. Here we use electrophysiological and behavioural experiments to reveal lapses in memory recall at 30 min and 2 h post conditioning. We show that only during these lapses is consolidation of long-term memory susceptible to interruption by external disturbance. These shared time points of memory lapse and susceptibility correspond to transitions between different phases of memory that have different molecular requirements. We propose that during periods of molecular transition memory recall is weakened, allowing novel sensory cues to block the consolidation of long-term memory. PMID:23481386

  12. Susceptibility of memory consolidation during lapses in recall.

    Science.gov (United States)

    Marra, Vincenzo; O'Shea, Michael; Benjamin, Paul R; Kemenes, Ildikó

    2013-01-01

    Memories that can be recalled several hours after learning may paradoxically become inaccessible for brief periods after their formation. This raises major questions about the function of these early memory lapses in the structure of memory consolidation. These questions are difficult to investigate because of the lack of information on the precise timing of lapses. However, the use of a single-trial conditioning paradigm in Lymnaea solves this problem. Here we use electrophysiological and behavioural experiments to reveal lapses in memory recall at 30 min and 2 h post conditioning. We show that only during these lapses is consolidation of long-term memory susceptible to interruption by external disturbance. These shared time points of memory lapse and susceptibility correspond to transitions between different phases of memory that have different molecular requirements. We propose that during periods of molecular transition memory recall is weakened, allowing novel sensory cues to block the consolidation of long-term memory.

  13. Autobiographical thinking interferes with episodic memory consolidation.

    Directory of Open Access Journals (Sweden)

    Michael Craig

    Full Text Available New episodic memories are retained better if learning is followed by a few minutes of wakeful rest than by the encoding of novel external information. Novel encoding is said to interfere with the consolidation of recently acquired episodic memories. Here we report four experiments in which we examined whether autobiographical thinking, i.e. an 'internal' memory activity, also interferes with episodic memory consolidation. Participants were presented with three wordlists consisting of common nouns; one list was followed by wakeful rest, one by novel picture encoding and one by autobiographical retrieval/future imagination, cued by concrete sounds. Both novel encoding and autobiographical retrieval/future imagination lowered wordlist retention significantly. Follow-up experiments demonstrated that the interference by our cued autobiographical retrieval/future imagination delay condition could not be accounted for by the sound cues alone or by executive retrieval processes. Moreover, our results demonstrated evidence of a temporal gradient of interference across experiments. Thus, we propose that rich autobiographical retrieval/future imagination hampers the consolidation of recently acquired episodic memories and that such interference is particularly likely in the presence of external concrete cues.

  14. Stages of Agricultural Land Consolidation in Ukraine with Consideration for International Best Practices

    Directory of Open Access Journals (Sweden)

    Popov Andriy S.

    2017-03-01

    Full Text Available The aim of the article is to develop recommendations on defining stages of consolidation of agricultural land in Ukraine on the basis of the best international practices. The analysis, systematization and generalization of scientific works of domestic and foreign scientists made it possible to determine a possible order of land consolidation in Ukraine and provide a detailed description of each stage. As a result of the research, the following main stages of land consolidation were proposed: the initiation, inventory, planning, implementation and final one. Each of these stages is considered consistently with justification of its expediency, the list of necessary measures and land management documentation, presentation of practical examples from different countries of the world. It is determined that each stage of the land consolidation procedure should be conducted in compliance with the principle of openness, which ensures the involvement of the maximum number of landowners/land users and protection of their interests, creates a positive attitude of the society towards land consolidation. A structural and logical model of the procedure for consolidating agricultural land, which clearly reflects the stages and activities of its implementation, is drawn up. There presented recommendations on the need to introduce new land management documentation for land consolidation with a detailed description of their essence. The relevance of further studies of the procedure for the agricultural land consolidation is in bringing a flexible, simple, cost-effective and short-term approach to its implementation.

  15. Thermal and loading effects on soil parameters during consolidation - Vacherie salt dome

    International Nuclear Information System (INIS)

    Baysal, D.F.; Tumay, M.T.

    1983-07-01

    Tiltmeters were installed at Vacherie dome to record possible domal movement. Tests were conducted to determine the effects of four factors on the soil consolidation process: temperature, preconsolidation stress, stress increment ratio, and soil type. These, and related experiments, also provided data useful for any future finite element analyses of near-surface effects over Vacherie dome. The four soil factors were tested in a pattern pre-determined by the Graeco-Latin Square Model of data collection and analysis. Results of the statistical analyses showed that soil type was the most important factor in the consolidation process. Soil temperatures affected the duration of consolidation, but not the amount of consolidation. Preconsolidation and stress increment ratio had the opposite effect, the latter being the least important factor in the soil consolidation process. Results of this study imply that the soils around the tiltmeter sites genrally respond to effects that can be associated with natural phenomenon, e.g., rainfall

  16. Hydrostatic and shear consolidation tests with permeability measurements on Waste Isolation Pilot Plant crushed salt

    International Nuclear Information System (INIS)

    Brodsky, N.S.

    1994-03-01

    Crushed natural rock salt is a primary candidate for use as backfill and barrier material at the Waste Isolation Pilot Plant (WIPP) and therefore Sandia National Laboratories (SNL) has been pursuing a laboratory program designed to quantify its consolidation properties and permeability. Variables that influence consolidation rate that have been examined include stress state and moisture content. The experimental results presented in this report complement existing studies and work in progress conducted by SNL. The experiments described in this report were designed to (1) measure permeabilities of consolidated specimens of crushed salt, (2) determine the influence of brine saturation on consolidation under hydrostatic loads, and 3) measure the effects of small applied shear stresses on consolidation properties. The laboratory effort consisted of 18 individual tests: three permeability tests conducted on specimens that had been consolidated at Sandia, six hydrostatic consolidation and permeability tests conducted on specimens of brine-saturated crushed WIPP salt, and nine shear consolidation and permeability tests performed on crushed WIPP salt specimens containing 3 percent brine by weight. For hydrostatic consolidation tests, pressures ranged from 1.72 MPa to 6.90 MPa. For the shear consolidation tests, confining pressures were between 3.45 MPa and 6.90 MPa and applied axial stress differences were between 0.69 and 4.14 MPa. All tests were run under drained conditions at 25 degrees C

  17. The Roles of Cortical Slow Waves in Synaptic Plasticity and Memory Consolidation

    OpenAIRE

    Miyamoto, Daisuke; Hirai, Daichi; Murayama, Masanori

    2017-01-01

    Sleep plays important roles in sensory and motor memory consolidation. Sleep oscillations, reflecting neural population activity, involve the reactivation of learning-related neurons and regulate synaptic strength and, thereby affect memory consolidation. Among sleep oscillations, slow waves (0.5–4 Hz) are closely associated with memory consolidation. For example, slow-wave power is regulated in an experience-dependent manner and correlates with acquired memory. Furthermore, manipulating slow...

  18. The Roles of Protein Expression in Synaptic Plasticity and Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Tali eRosenberg

    2014-11-01

    Full Text Available The amount and availability of proteins are regulated by their synthesis, degradation, and transport. These processes can specifically, locally, and temporally regulate a protein or a population of proteins, thus affecting numerous biological processes in health and disease states. Accordingly, malfunction in the processes of protein turnover and localization underlies different neuronal diseases. However, as early as a century ago, it was recognized that there is a specific need for normal macromolecular synthesis in a specific fragment of the learning process, memory consolidation, which takes place minutes to hours following acquisition. Memory consolidation is the process by which fragile short-term memory is converted into stable long-term memory. It is accepted today that synaptic plasticity is a cellular mechanism of learning and memory processes. Interestingly, similar molecular mechanisms subserve both memory and synaptic plasticity consolidation. In this review, we survey the current view on the connection between memory consolidation processes and proteostasis, i.e., maintaining the protein contents at the neuron and the synapse. In addition, we describe the technical obstacles and possible new methods to determine neuronal proteostasis of synaptic function and better explain the process of memory and synaptic plasticity consolidation.

  19. Initial Assessment of the Consolidation of Chalcogels into a Viable Waste Form

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Brian J.; Lepry, William C.

    2012-08-31

    This report provides some preliminary data for the consolidation of chalcogen-based aerogels. The chalcogels tested to date at PNNL show great promise as iodine sorbents and preliminary consolidation research shows that they can be melted into a phase-pure glass at moderate temperatures. The preliminary consolidation experiments show that these materials might attack fused quartz so an alternative crucible material will likely need to be used to prevent this. The next steps will be to • Consider melting other chalcogel chemistries, e.g., Sn-Sb-S, Ge-Sn-S chalcogels • Consider melting chalcogels with adsorbed iodine to monitor iodine loss during melting • Optimize the consolidation temperatures to minimize the iodine loss and volatilization

  20. 105KE and 105KW Basins fuel and sludge consolidation study, summary report

    International Nuclear Information System (INIS)

    Gant, R.G.

    1994-01-01

    This study is a summary report that examines and evaluates the feasibility of consolidating irradiated fuel and sludge currently in KE Basin with that in the KW Basin. This study was conducted in support of TPA Milestone (target date) M-34-00-T03. The report summarizes three supporting engineering studies involving: (1) spent fuel consolidation into the single basin, (2) transport of the encapsulated fuel between KE and KW Basins, and (3) dispositioning contaminated water remaining in KE Basin. From the three reports, and preferred storage method, transfer method and water disposition method were defined. These consolidation methods were then evaluated against the no action alternative of continued storage using both KE and KW Basins. The report concluded that the fuel and sludge currently stored in KE Basin not be consolidated in the KW Basin, primarily due to increased cost and radiation exposure required to consolidate the fuel and sludge. Consolidation is more attractive for storage periods beyond the year 2002, which is the study period of the report

  1. Proposal for Land Consolidation Project Solutions for Selected Problem Areas

    Science.gov (United States)

    Wojcik-Len, Justyna; Strek, Zanna

    2017-12-01

    One of the economic tools for supporting agricultural policy are the activities implemented under the Rural Development Program (RDP). By encouraging agricultural activities and creating equal opportunities for development of farms, among others in areas with unfavourable environmental conditions characterized by low productivity of soils exposed to degradation, decision makers can contribute to improving the spatial structure of rural areas. In Poland, one of the major concerns are agricultural problem areas (regions). In view of this situation, the aim of this article was to characterize the problem areas in question and propose land consolidation project solutions for selected fragments of those areas. This paper presents the results of a review of literature and an analysis of geodetic and cartographic data regarding the problem areas. The process of land consolidation, which is one of the technical and legal instruments supporting the development of rural areas, was characterized. The study allowed the present authors to establish criteria for selecting agricultural problem areas for land consolidation. To develop a proposal for rational management of the problem areas, key general criteria (location, topography, soil quality and usefulness) and specific criteria were defined and assigned weights. A conception of alternative development of the agricultural problem areas was created as part of a land consolidation project. The results were used to create a methodology for the development of agricultural problem areas to be employed during land consolidation in rural areas. Every agricultural space includes areas with unfavourable environmental and soil conditions determined by natural or anthropogenic factors. Development of agricultural problem areas through land consolidation should take into account the specific functions assigned to these areas in land use plans, as well as to comply with legal regulations.

  2. Strata consolidation (Report on ECSC contract 6220-AB/1/102)

    Energy Technology Data Exchange (ETDEWEB)

    1978-01-01

    The development of an injection agent based on Sorel cement with a magnesia binder is discussed. The properties of the binder are discussed including its adherence properties. The extraordinary fluidity of the magnesia binder permits a transport of the binder ready for application for a distance of 800 m, provided the pipelines used do not have a diameter below 25 mm. The magnesia binder still fills cracks and fissures with a width of 0.1 mm. The injection method was used in the mines of Saarbergwerke AG mainly for consolidation of running out coal faces. Normally, it was possible to consolidate the coal in thick seams by use of magnesia binder. Reasons for unsatisfactory consolidating results in some tests at the Ruhr are different structure and wettability of the Ruhr coal, presumably. Adjoining rock, especially shaly clay, could be consolidated so well with magnesia binder that the original rock context could be restored. Trials to seal permeable rock formations, led to the development of control methods enabling a quantitative assessment of injections underground. (In German)

  3. Sealed source and device removal and consolidation feasibility study

    International Nuclear Information System (INIS)

    Ward, J.E.; Carter, J.G.; Meyers, R.L.

    1993-02-01

    The purpose of this study is to assess the feasibility of removing Greater-Than-Class C (GTCC) sealed sources from their containment device and consolidating them for transport to a storage or disposal facility. A sealed source is a sealed capsule containing a radioactive material that is placed in a device providing radioactive containment. It is used in the medical, industrial, research, and food-processing communities for calibrating, measuring, gauging, controlling processes, and testing. This feasibility study addresses the key operational, safety, regulatory, and financial requirements of the removal/consolidation process. This report discusses the process to receive, handle, repackage, and ship these sources to an interim or dedicated storage facility until a final disposal repository can be built and become operational (∼ c. 2010). The study identifies operational and facility requirements to perform this work. Hanford, other DOE facilities, and private hot-cell facilities were evaluated to determine which facilities could perform this work. The personnel needed, design and engineering, facility preparation, process waste disposal requirements, and regulatory compliance were evaluated to determine the cost to perform this work. Cost requirements for items that will have to meet future changing regulatory requirements for transportation, transportation container design and engineering, and disposal were not included in this study. The cost associated with in-process consolidation of the sealed sources reported in this study may have not been modified for inflation and were based on 1992 dollars. This study shows that sealed source consolidation is possible with minimal personnel exposure, and would reduce the risk of radioactive releases to the environment. An initial pilot-scale operation could evaluate the possible methods to reduce the cost and consolidate sources

  4. Consolidity: Moving opposite to built-as-usual systems practices

    Directory of Open Access Journals (Sweden)

    Hassen Taher Dorrah

    2013-06-01

    Full Text Available With the recent uncovering of the mystery of consolidity as an inner property of systems, it is demonstrated that this notion is an indispensable pillar of systems modeling, analysis, design and building. Based on the opposite mathematical relation between consolidity versus stability and controllability, a new conceptual life cycle (change pathway graph for natural and man-made built-as-usual systems is presented and thoroughly discussed. For the conceptual cycle development progress, it is logically conceived that system behavior changes rate has not accidentally happened, but is relatively influenced at the point of progress by the associated direct system consolidity index corresponding to the acting on-the-spot varying environments or effects. Such conceptual graph represents a real research advancement indicating that we have to move opposite to current systems building practices for solving many real life enigmatic problems. It is illustrated using stabilization of inverted pendulum problem that it is amenable by cleverly manipulating systems structure and parameters to attain new designed systems with aggregates of superiority of consolidity, stability and controllability principle. It is recommended that we have to seek new generation of innovative non-conventional systems structures moving opposite to conventional built-as-usual system practices that can enable providing directly such three aggregates of superiority requirements as their built-in self property. This will open the door towards solving many real life challenging dilemmas in various sciences and disciplines, such as engineering, space sciences, medicine, pharmacology, biology, ecology, life sciences, economy, operations research, humanities and social sciences that are believed to be attributed due to their systems inferior consolidity.

  5. Industrial tests of rock consolidation for fighting floor swelling

    Energy Technology Data Exchange (ETDEWEB)

    Pirskii, A A; Stovpnik, S N [KPI (USSR)

    1990-04-01

    Reports on investigations into the mechanism of floor swelling in main roadways and into rock mass stabilization by consolidating fluid injection combined with blasting. The principal cause of deterioration in the stability of workings is considered to be the state of stress in the rock mass, rock destruction in side walls where rock blocks are being pressed into the floor while the floor rock is squeezed out into the working space. A case study of fluid injection combined with blasting applied in several mines in the Donbass is presented where holes were drilled 1.5-3 m deep and explosive charges of 0.07-0.1 kg/hole and injection of hardening solutions (0.56-0.83 m{sup 3}/m of workings) were applied. As a result floor swelling rates were reduced by up to about 5 times (e.g. from 2.5 mm/d to 0.5 mm/d.). The period of maintenence free upkeep of workings was extended to 6-8 years. The economic effect in maintenance of 1 m of workings was 11.7 rubles for floor consolidation without sidewall bolting and 51.4 rubles for floor consolidation combined with sidewall bolting. Recommendations that concern the technology of floor consolidation by fluid injection and blasting are made. 4 refs.

  6. Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

    International Nuclear Information System (INIS)

    Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

    1996-01-01

    Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

  7. SOME DISCLOSURE ASPECTS REGARDING CONSOLIDATED FINANCIAL STATEMENTS

    Directory of Open Access Journals (Sweden)

    Cirstea Andreea

    2013-07-01

    Full Text Available The purpose of this article is to analyze the current state of consolidated reporting practice harmonization concerning the choice of presenting the income statement, the changes in equity, the methods used for presenting the cash flow statement, the extant methods for evaluating and reporting goodwill, the extant methods in which jointly controlled entities are accounted in the consolidated financial statements, or the choice for recognizing investments in subsidiaries, jointly controlled entities and associates in the separate statements of the parent company. In order to achieve our goal we selected the first 10 groups, in order of their capitalization value, that were listed on each of the following capital markets: London Stock Exchange, NYSE Euronext (Paris Stock Exchange and Deutsche Börse (Frankfurt Stock Exchange and we analyzed, in a qualitative and in a quantitative manner, for a period of six years starting with 2007, their consolidated financial statements with the design to establish exactly which of the aspects stated in the International Financial Reporting Standards were being used for the items presented above. In order to complete the empirical research part of the paper that addresses from a comparative perspective the evaluation of the degree of material harmony between the reporting practices of groups listed on the three stock exchanges above-mentioned, we used statistical and mathematical methods represented by the I Index first described by Van der Tas. Taking into account the fact that since 2005 all listed companies on the European stock exchanges were required to adopt the international accounting standards for their consolidated financial disclosures, the degree of material harmony was studied only in reference to those requirements that presented two methods or possibilities of disclosure.Our findings suggest that the groups analyzed present a high degree of material harmonization with respect to the reporting

  8. Consolidated techniques for groups of enterprises with complex structure

    Directory of Open Access Journals (Sweden)

    Cristina Ciuraru-Andrica

    2009-12-01

    Full Text Available The preparation and disclosure of the financial statements of a group of enterprises involves some consolidation techniques. The Literature presents many techniques, but in practice are used two of them. They will be described first of all in a particular manner and after that in a comparative one. The group of entities can choose one of these techniques, the final result (the consolidated financial statements being the same, whatever the option.

  9. Consolidation by Prefabricated Vertical Drains with a Threshold Gradient

    OpenAIRE

    Xiao Guo; Kang-He Xie; Yue-Bao Deng

    2014-01-01

    This paper shows the development of an approximate analytical solution of radial consolidation by prefabricated vertical drains with a threshold gradient. To understand the effect of the threshold gradient on consolidation, a parametric analysis was performed using the present solution. The applicability of the present solution was demonstrated in two cases, wherein the comparisons with Hansbo’s results and observed data were conducted. It was found that (1) the flow with the threshold gradie...

  10. Magnetic properties of ultrafine-grained cobalt samples obtained from consolidated nanopowders

    Energy Technology Data Exchange (ETDEWEB)

    Fellah, F.; Cherif, S.M.; Schoenstein, F.; Jouini, N.; Dirras, G. [LSPM (CNRS-UPR 3407), Universite Paris 13, 99 av. J.B. Clement, 93430 Villetaneuse (France); Bouziane, K. [Department of Physics, College of Science, Sultan Qaboos University, P.O. Box 36, Al-Khodh 123 (Oman)

    2011-08-15

    Co powders having nominal average particle size of 50 and 240 nm were synthesized using a polyol method and then consolidated by hot isostatic pressing (HIP) or the emerging spark plasma sintering (SPS) compaction processes. Bulk polycrystalline aggregates were obtained, having average grain sizes of about 200 and 300 nm, respectively. It is found that both nanoparticles and consolidated samples exhibit a soft ferromagnetic behavior. The magnetization reversal likely occurs by nucleation/propagation process. However, a curling process can be involved in the magnetization reversal for the smaller particles. The dynamic measurements provide for the consolidated samples magnetic parameters corresponding to bulk cobalt with vanishing anisotropy. The contribution of the intergranular region is found to be negligible. We can infer that the used consolidation routes insure a good magnetic interfacial contact between the particles. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. Consolidation ou résistance à l'interférence ?Etude de la contribution des états de sommeil aux processus post-apprentissage de consolidation et de résistance à l'interférence lexicale et émotionnelle rétroactive./Consolidation or protection against interference? an investigation of sleep stages contribution in post-learning memory consolidation and protection against lexical and emotional retroactive interference processes.

    OpenAIRE

    Deliens, Gaétane

    2013-01-01

    Although a relative consensus exists about the contribution of post-learning sleep in the consolidation of novel information in long term memory, the definition of the respective contributions of sleep stages in memory consolidation processes remains a matter of debates. Scrima (1982) proposed the hypothesis that Slow Waves Sleep (SWS) contributes preventing retroactive interference on recently acquired information, whereas Rapid Eyes Movement sleep (REM) contributes consolidating this inform...

  12. 76 FR 6813 - Agency Information Collection Activities: Comment Request for the Consolidated Consumers' Report...

    Science.gov (United States)

    2011-02-08

    ... Collection Activities: Comment Request for the Consolidated Consumers' Report (1 Form) AGENCY: U.S... Consolidated Consumers' Report. This collection consists of one form. This notice provides the public and other...: 9-4117-MA. Title: Consolidated Consumers' Report. Type of Request: Extension of a currently approved...

  13. WWER reactor pressure vessel embrittlement knowledge - a way forward for consolidation

    International Nuclear Information System (INIS)

    Von Estorff, U.; Brumovsky, M.

    2010-01-01

    Many stakeholders, such as Institutes, R and D Organisations, Regulators, Utilities, Governmental Organisations, have recognised the need for collecting, preserving, consolidating (validating), and disseminating nuclear knowledge (documents, competences and data), in order to make it easily accessible to future generations through modern informatics tools and training and education measures. A broad spectrum of components and technologies should be considered, i.e. reactor pressure vessel (RPV), piping, internals, steam generator, etc. regarding knowledge, material data and practices. In the long run, it will also support future decommissioning exercises of nuclear installations as a valuable knowledge source. In addition to the knowledge in each Member State, the IE produced a long standing record of results from its own institutional activities and even more through the participation to a large number of European Network partnership projects. It is important, besides preservation, to consolidate the enormous amount of scientific results produced since. Therefore, the IE has developed a method for consolidation of nuclear knowledge. The method relays on the mobilisation of all identified leading experts in the EU in re-evaluating old knowledge and consolidating what is necessary to create training materials for the new generations. This method was applied for a pilot study for consolidating and preserving WWER RPV safety related knowledge, which is scattered in many countries and in different languages, facing a serious issue in terms of getting lost. This initiative could be the start of a wider Nuclear Knowledge Preservation and Consolidation activity. Experience gained and lessons learnt from the first exercise will be presented in this paper. (authors)

  14. Preparation of an annual report for a consolidated radioisotope licence

    International Nuclear Information System (INIS)

    1985-01-01

    A consolidated radioisotope licence is a single license issued by the Atomic Energy Control Board (AECB) to an institution having many users of radioactive materials. The licence is issued when the institution has fulfilled the requirements set by the AECB and has implemented policies and procedures which will ensure the maintenance of an effective radiation safety program. The consolidated licence is retained only if the results of AECB inspections are satisfactory -- or remedial action is taken promptly -- and if the institution reports regularly about the status of its radiation safety program. One aspect of this reporting procedure is an annual report. This guide describes the information that the AECB requires in the annual report. The guide applies primarily to universities and research institutions where a wide variety of radioisotope uses take place. The guide does not affect most other institutions or facilities, either because the nature and extent of their operations with radioactive materials do not lend themselves to consolidated licensing or because they are not licensed by the Radioisotopes and Transportation Division. (For example, this guide does not apply to reactors, to accelerators, or to waste management or uranium mining or refining facilities.) The information in the annual report should be specific to the consolidated radioisotope licence. Incidents, staff exposures, and waste associated with accelerators, research reactors, and waste management facilities should be excluded from this report unless they affected activities under the consolidated licence

  15. Municipal Consolidation: Theoretical Inquiry and Case Study - City of Iron River, MI

    OpenAIRE

    Martin, Joseph M.

    2006-01-01

    The City of Iron River was created as a consolidated municipality in the upper peninsula of Michigan during the late 1990's. The consolidation consisted of two cities and one village with a combined 2000 census population of 3,391. Persistent population loss, combined with the decline of the economic base, reduced the viability of the individual municipal governments, placing consolidation at the forefront of options. The analysis of small, rural municipalities is outside the focus of most co...

  16. Acute exercise and motor memory consolidation

    DEFF Research Database (Denmark)

    Thomas, Richard; Korsgaard Johnsen, Line; Geertsen, Svend Sparre

    2016-01-01

    where low to moderate intensities may be more suitable. The aim of this study was to investigate the role of intensity in mediating the effects of acute cardiovascular exercise on motor skill learning. We investigated the effects of different exercise intensities on the retention (performance score...... an important role in modulating the effects that a single bout of cardiovascular exercise has on the consolidation phase following motor skill learning. There appears to be a dose-response relationship in favour of higher intensity exercise in order to augment off-line effects and strengthen procedural memory.......A single bout of high intensity aerobic exercise (~90% VO2peak) was previously demonstrated to amplify off-line gains in skill level during the consolidation phase of procedural memory. High intensity exercise is not always a viable option for many patient groups or in a rehabilitation setting...

  17. 7 CFR 3015.311 - Simplification, consolidation, or substitution of State plans.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Simplification, consolidation, or substitution of... (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE UNIFORM FEDERAL ASSISTANCE... Simplification, consolidation, or substitution of State plans. (a) As used in this section: (1) Simplify means...

  18. Chromatic reintegration of historical mortars with lime-based pozzolanic consolidant products

    NARCIS (Netherlands)

    Borsoi, G.; Pascoal, P.; Pinto, J.P.; Veiga, R.; Faria, P.; Santos Silva, A.

    2013-01-01

    The consolidation process of old renders with loss of cohesion is nowadays performed usually with inorganic compatible products, such as calcium or barium hydroxide or ethyl silicate. The use of organic consolidants as acrylic or vinilic resins is discouraged due to its physico-chemical

  19. Consolidation of the LHC superconducting magnets and circuits during LS1

    International Nuclear Information System (INIS)

    Tock, J.P.

    2012-01-01

    All the activities necessary to consolidate the LHC superconducting magnets and circuits are presented, especially the consolidation of the main splices, replacement of weak cryo-magnets, the consolidation of the DFBAs (electrical feed-boxes) and the special interventions. For each of them, the baseline strategy is presented, highlighting the reasons that led to these choices and the remaining risk level. In particular, the progress of the work of the LHC Splices Task Force, the recommendations of the second LHC Splices Review (November 2011) and their analysis are reported. Finally, the work planning, the organization chart and the associated resources are detailed. (author)

  20. Possibility of "superfast" consolidation of long-term memory.

    Science.gov (United States)

    Podolski IYa

    1998-01-01

    Two new behavioural tests in rats are described which demonstrate the fast consolidation of the long-term memory (LTM) in a dangerous natural situation (water escape). It is shown that after one-trial learning of the motor skill (jumping out of the water), long-term memory traces are retained without forgetting and are resistant to the blockade of M-cholinoreceptors by scopolamine (2 mg/kg) and of D1/D2 dopamine receptors by haloperidol (10 mg/kg) as well as electroconvulsive shock applied tank wall, learning of necessary motor skills, automatization and minimization of the skilled movements in 1.5-3.0 min, after 5 to 7 trials at two-second intervals (superfast learning) is demonstrated. It is suggested that the superfast consolidation of LTM (several minutes) is possible in life-threatening situations, the necessary time being 1-2 orders of magnitude less than it is generally accepted in the modern theories of memory. The proposed behavioural models may be helpful in investigation of some fundamental physiological and molecular mechanisms of stable neuronal interactions, as a basis for LTM consolidation.

  1. Divulgación del Programa Consolider-GTC

    Science.gov (United States)

    Ruiz Zelmanovitch, N.; Mass Hesse, M.; Alfaro, E.

    2013-05-01

    The Gran Telescopio Canarias (GTC) is the biggest telescope of its class in the world. The CONSOLIDER INGENIO 2010-GTC project, First Science with the GTC: Spanish Astron- omy on the Forefront of the European Astronomy, funded by the Spanish Ministry of Science and Innovation, MICINN (now the Ministry of Economy and competitiveness, MINECO) has used the GTC to: (i) obtain leading science with its data, (ii) increase the involvement of the Spanish astronomical community in developing astronomical instrumentation, (iii) get an important Spanish participation in the new extremely large telescopes generation (ELTs), and (iv) make outreach and communicating to the society the main results. The project CONSOLIDER INGENIO 2010-GTC is structured and defined by objectives: 1) GTC: To optimize the GTC and its instruments; 2) SCIENCE: To develop leading science with the GTC; 3) E-ELT: To take advantage of the technological experience obtained with the GTC for the new generation of giant telescopes; 4) INSTRUMENTATION: To promote the Spanish participation in the new instrument developments for the GTC, VLT and the future ELTs; 5) EDUCATION: International School for Advanced Instrumentation (IScAI); and 6) OUTREACH: Outreach and communication of the project scientific results. This poster resumes five years of science communication around the Consolider-GTC project.

  2. Influence of prepreg characteristics on stamp consolidation

    Science.gov (United States)

    Slange, T. K.; Warnet, L. L.; Grouve, W. J. B.; Akkerman, R.

    2017-10-01

    Stamp forming is a rapid manufacturing technology used to shape flat blanks of thermoplastic composite material into three-dimensional components. The development of automated lay-up technologies further extends the applicability of stamp forming by allowing rapid lay-up of tailored blanks and partial preconsolidation. This partial preconsolidation makes the influence of prepreg more critical compared to conventional preconsolidation methods which provide full preconsolidation. This paper aims to highlight consolidation challenges that can appear when stamp forming blanks manufactured by automated lay-up. Important prepreg characteristics were identified based on an experimental study where a comparison was made between various prepreg in their as-received, deconsolidated and stamp consolidated state. It was found that adding up small thickness variations across the width of a prepreg when stacking plies into a blank by automated lay-up can cause non-uniform consolidation. Additionally, deconsolidation of the prepreg does not seem to obstruct interlaminar bonding, while intralaminar voids initially present in a prepreg cannot be removed during stamp forming. An additional preconsolidation step after automated lay-up seems necessary to remove blank thickness variations and intralaminar voids for the current prepregs. Eliminating this process step and the successful combination of rapid automated lay-up and stamp forming requires prepregs which are void-free and have less thickness variation.

  3. Linking new information to a reactivated memory requires consolidation and not reconsolidation mechanisms.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available A new memory is initially labile and becomes stabilized through a process of consolidation, which depends on gene expression. Stable memories, however, can again become labile if reactivated by recall and require another phase of protein synthesis in order to be maintained. This process is known as reconsolidation. The functional significance of the labile phase of reconsolidation is unknown; one hypothesis proposes that it is required to link new information with reactivated memories. Reconsolidation is distinct from the initial consolidation, and one distinction is that the requirement for specific proteins or general protein synthesis during the two processes occurs in different brain areas. Here, we identified an anatomically distinctive molecular requirement that doubly dissociates consolidation from reconsolidation of an inhibitory avoidance memory. We then used this requirement to investigate whether reconsolidation and consolidation are involved in linking new information with reactivated memories. In contrast to what the hypothesis predicted, we found that reconsolidation does not contribute to the formation of an association between new and reactivated information. Instead, it recruits mechanisms similar to those underlying consolidation of a new memory. Thus, linking new information to a reactivated memory is mediated by consolidation and not reconsolidation mechanisms.

  4. Cyclic behavior of self-consolidated concrete.

    Science.gov (United States)

    2014-08-01

    This reports highlights on the production of Self-Consolidating concrete using local materials from Las Vegas, Nevada. 4 SCC : mixtures were worked on with 2 different levels of FA replacement and the inclusion of superplasticizers, ADVA 195 and V-MA...

  5. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 4 discusses the following topics: Rod Compaction/Loading System Test Results and Analysis Report; Waste Collection System Test Results and Analysis Report; Waste Container Transfer Fixture Test Results and Analysis Report; Staging and Cutting Table Test Results and Analysis Report; and Upper Cutting System Test Results and Analysis Report

  6. Auto consolidated cohesive sediments erosion

    International Nuclear Information System (INIS)

    Ternat, F.

    2007-02-01

    Pollutants and suspended matters of a river can accumulate into the sedimentary column. Once deposited, they are submitted to self-weight consolidation processes, ageing and burying, leading to an increase of their erosion resistance. Pollutant fluxes can be related to sedimentary fluxes, determined by threshold laws. In this work, an erosion threshold model is suggested by introducing a cohesion force into the usual force balance. A model of cohesion is developed on the basis of interactions between argillaceous cohesive particles (clays), particularly the Van der Waals force, whose parameterization is ensured by means of granulometry and porosity. Artificial erosion experiments were performed in a recirculating erosion flume with natural cored sediments where critical shear stress measurements were performed. Other analyses provided granulometry and porosity. The results obtained constitute a good database for the literature. The model is then applied to the experimental conditions and gives good agreement with measurements. An example of the accounting for self-weight consolidation processes is finally suggested, before finishing on a Mohr like diagram dedicated to soft cohesive sediment erosion. (author)

  7. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 5 discusses the following topics: Lower Cutting System Test Results and Analysis Report; NFBC Loading System Test Results and Analysis Report; Robotic Bridge Transporter Test Results and Analysis Report; RM-10A Remotec Manipulator Test Results and Analysis Report; and Manipulator Transporter Test Results and Analysis Report

  8. The delivery dispatching problem with time windows for urban consolidation centers

    NARCIS (Netherlands)

    van Heeswijk, W.J.A.; Mes, Martijn R.K.; Schutten, Johannes M.J.

    2015-01-01

    This paper addresses the dispatch decision problem faced by an urban consolidation center. The center receives orders according to a stochastic arrival process, and dispatches them for the last-mile distribution in batches. The operator of the center aims to fi nd the cost-minimizing consolidation

  9. SPECIFIC OPERATIONS FOR ACCOUNTS’ HOMOGENIZATION WITH A VIEW TO CONSOLIDATION

    Directory of Open Access Journals (Sweden)

    Mihai Deju

    2017-12-01

    Full Text Available The preparation of annual consolidated financial statements by group companies represents a relatively new problematic issue for regulating bodies, the world of the academia, as well as for accounting practitioners. The current national and international accounting standards undergo a continuous change and updating to the economic and judicial reality of the business environment which, in turn, goes through a permanent transformation as a result of the globalization of national economies. These novelties raise the necessity of debates organised by accounting specialists with the aim of finding solutions that respect legal regulations related to the preparation of financial statements for consolidation. The present article approaches accounting aspects related to the operation of adjusting individual financial statements that are the object of consolidation.

  10. A BRIEF ANALYSIS OF PUBLIC SECTOR CONSOLIDATED FINANCIAL STATEMENTS RESEARCHES

    Directory of Open Access Journals (Sweden)

    Andreea CÎRSTEA

    2015-12-01

    Full Text Available The purpose of the paper is to track the evolution of this specific topic of consolidated financial statements in the public sector, in order to be able to present a global picture of the actual knowledge stage of this issue at international level. The study conducted for reaching the proposed objective is a quantitative one. We tried to find out how this issue of public sector consolidated financial statements has sparked the interest of researchers around the world and when the issue was most debated. We concluded that the research of consolidated financial statements in the public sector is in its infancy and nowadays the topic starts to be more and more in the attention of the researchers in this field.

  11. Fear memory consolidation in sleep requires protein kinase A.

    Science.gov (United States)

    Cho, Jiyeon; Sypniewski, Krzysztof A; Arai, Shoko; Yamada, Kazuo; Ogawa, Sonoko; Pavlides, Constantine

    2018-05-01

    It is well established that protein kinase A (PKA) is involved in hippocampal dependent memory consolidation. Sleep is also known to play an important role in this process. However, whether sleep-dependent memory consolidation involves PKA activation has not been clearly determined. Using behavioral observation, animals were categorized into sleep and awake groups. We show that intrahippocampal injections of the PKA inhibitor Rp-cAMPs in post-contextual fear conditioning sleep produced a suppression of long-term fear memory, while injections of Rp-cAMPs during an awake state, at a similar time point, had no effect. In contrast, injections of the PKA activator Sp-cAMPs in awake state, rescued sleep deprivation-induced memory impairments. These results suggest that following learning, PKA activation specifically in sleep is required for the consolidation of long-term memory. © 2018 Cho et al.; Published by Cold Spring Harbor Laboratory Press.

  12. European defence industry consolidation and domestic procurement bias

    DEFF Research Database (Denmark)

    Kluth, Michael Friederich

    2017-01-01

    How have European cross-border defence industrial mergers and acquisitions affected domestic procurement bias among the major EU powers? This article departs from the findings of Andrew Moravcsik more than two decades ago suggesting that major West European states had no ingrained preferences...... for defence industrial autarchy. When cross-national armament projects were derailed, this could be attributed to political efforts of national defence industrial champions favouring purely domestic projects. As former national champions join pan-European defence groups, their preferences are likely modified......-border defence industry consolidation will be analysed. Procurement bias is assessed in two industry segments characterised by pervasive consolidation....

  13. Consolidation of renders and plasters

    Czech Academy of Sciences Publication Activity Database

    van Hees, R.; Veiga, R.; Slížková, Zuzana

    2017-01-01

    Roč. 50, č. 1 (2017), s. 50-65 ISSN 1359-5997 R&D Projects: GA MŠk(CZ) LO1219 Keywords : consolidants * plasters * requirements * selection * assessment Subject RIV: AL - Art, Architecture, Cultural Heritage OBOR OECD: Materials engineering Impact factor: 2.607, year: 2016 http://link.springer.com/article/10.1617/s11527-016-0894-5

  14. [Theories and methodologies of engineering designs on sustainable agricultural land consolidation project--a case study of Xuemeiyang land consolidation project in Changtai County, Fujian Province].

    Science.gov (United States)

    Ye, Yanmei; Wu, Cifang; Cheng, Chengbiao; Qiu, Lingzhang; Huang, Shengyu; Zheng, Ruihui

    2002-09-01

    The concept and characteristics of engineering designs on sustainable agricultural land consolidation project were discussed in this paper. Principles, basic methods and procedures of engineering designs on agricultural land consolidation project were put forward, which were successfully adopted for designing agricultural land consolidation in Xuemeiyang region of Changtai County, including diversity designs of sustainable land use, engineering designs of soil improvement, roads, ditches, and drains for protecting existent animal environments, and design of ecological shelter-forests in farmland. Moreover, from sustainable economic, ecological and social points, the results of these engineering designs were evaluated based on fouteen important indexes. After carrying out these engineeringdesigns, the eco-environments and agricultural production conditions were significantly improved, and the farm income was increased in planned regions.

  15. 76 FR 42461 - Consolidated Delegation of Authority to the General Counsel

    Science.gov (United States)

    2011-07-18

    ... demands from the courts or other authorities; 24 CFR Part 15. 3. Designating the General Counsel as the... seq. 6. Authorizing the General Counsel to initiate a civil money penalty action pursuant to Sections... Consolidated Delegation of Authority to the General Counsel and Consolidated Redelegation of Authority to the...

  16. Relief memory consolidation requires protein synthesis within the nucleus accumbens.

    Science.gov (United States)

    Bruning, Johann E A; Breitfeld, Tino; Kahl, Evelyn; Bergado-Acosta, Jorge R; Fendt, Markus

    2016-06-01

    Relief learning refers to the association of a stimulus with the relief from an aversive event. The thus-learned relief stimulus then can induce, e.g., an attenuation of the startle response or approach behavior, indicating positive valence. Previous studies revealed that the nucleus accumbens is essential for the acquisition and retrieval of relief memory. Here, we ask whether the nucleus accumbens is also the brain site for consolidation of relief memory into a long-term form. In rats, we blocked local protein synthesis within the nucleus accumbens by local infusions of anisomycin at different time points during a relief conditioning experiment. Accumbal anisomycin injections immediately after the relief conditioning session, but not 4 h later, prevented the consolidation into long-term relief memory. The retention of already consolidated relief memory was not affected by anisomycin injections. This identifies a time window and site for relief memory consolidation. These findings should complement our understanding of the full range of effects of adverse experiences, including cases of their distortion in humans such as post-traumatic stress disorder and/or phobias. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The consolidation of implicit sequence memory in obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Eszter Csabi

    Full Text Available Obstructive Sleep Apnea (OSA Syndrome is a relatively frequent sleep disorder characterized by disrupted sleep patterns. It is a well-established fact that sleep has beneficial effect on memory consolidation by enhancing neural plasticity. Implicit sequence learning is a prominent component of skill learning. However, the formation and consolidation of this fundamental learning mechanism remains poorly understood in OSA. In the present study we examined the consolidation of different aspects of implicit sequence learning in patients with OSA. We used the Alternating Serial Reaction Time task to measure general skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 10-hour offline period with sleep. Our data showed differences in offline changes of general skill learning between the OSA and control group. The control group demonstrated offline improvement from evening to morning, while the OSA group did not. In contrast, we did not observe differences between the groups in offline changes in sequence-specific learning. Our findings suggest that disrupted sleep in OSA differently affects neural circuits involved in the consolidation of sequence learning.

  18. Napping and the Selective Consolidation of Negative Aspects of Scenes

    Science.gov (United States)

    Payne, Jessica D.; Kensinger, Elizabeth A.; Wamsley, Erin; Spreng, R. Nathan; Alger, Sara; Gibler, Kyle; Schacter, Daniel L.; Stickgold, Robert

    2018-01-01

    After information is encoded into memory, it undergoes an offline period of consolidation that occurs optimally during sleep. The consolidation process not only solidifies memories, but also selectively preserves aspects of experience that are emotionally salient and relevant for future use. Here, we provide evidence that an afternoon nap is sufficient to trigger preferential memory for emotional information contained in complex scenes. Selective memory for negative emotional information was enhanced after a nap compared to wakefulness in two control conditions designed to carefully address interference and time-of-day confounds. Although prior evidence has connected negative emotional memory formation to rapid eye movement (REM) sleep physiology, we found that non-REM delta activity and the amount of slow wave sleep (SWS) in the nap were robustly related to the selective consolidation of negative information. These findings suggest that the mechanisms underlying memory consolidation benefits associated with napping and nighttime sleep are not always the same. Finally, we provide preliminary evidence that the magnitude of the emotional memory benefit conferred by sleep is equivalent following a nap and a full night of sleep, suggesting that selective emotional remembering can be economically achieved by taking a nap. PMID:25706830

  19. Combination vinblastine, prednisolone and toceranib phosphate for treatment of grade II and III mast cell tumours in dogs.

    Science.gov (United States)

    Olsen, Jaime A; Thomson, Maurine; O'Connell, Kathleen; Wyatt, Ken

    2018-05-24

    This retrospective study evaluates the progression-free interval and survival outcomes of 40 canine (Canis familiaris) patients with Patnaik grade II and III mast cell tumours treated with combination vinblastine, prednisolone and toceranib phosphate from 2011 to 2015. Patients were subdivided into three groups; patients who received neoadjuvant therapy for poorly operable lesions, patients who received adjuvant therapy following surgical resection and patients being palliated for gross metastatic disease. Median survival time (MST) for the neoadjuvant group was not reached. Median survival time for the remaining groups was 893 days and 218 days, respectively. This combination demonstrated response in 90% (26/29) patients with measurable disease. The predominant side effects related to this chemotherapy combination were gastrointestinal in origin. Further prospective studies are required to further validate the efficacy of this treatment protocol. © 2018 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.

  20. A case of acne fulminans in a patient with ulcerative colitis successfully treated with prednisolone and diaminodiphenylsulfone: a literature review of acne fulminans, rosacea fulminans and neutrophilic dermatoses occurring in the setting of inflammatory bowel disease.

    Science.gov (United States)

    Wakabayashi, Makiko; Fujimoto, Noriki; Uenishi, Toshiaki; Danno, Kiichiro; Tanaka, Toshihiro

    2011-01-01

    A 19-year-old Japanese man had been treated for ulcerative colitis for 2 years. He was admitted to our hospital with nodulocystic inflammatory papules and pustules on his face and chest, high-grade fever, arthralgia and general malaise. A biopsy specimen from a pustule showed prominent infiltration of neutrophils in the epidermis and dermis, particularly around hair follicles. We made a diagnosis of acne fulminans. The systemic administration of prednisolone at 30 mg daily for 1 week immediately improved his skin lesions and other symptoms; however, during tapering of prednisolone at 20 mg daily, skin lesions flared up. The addition of oral diaminodiphenylsulfone improved the skin lesions. Although there have been a few reports of acne fulminans associated with Crohn's disease, this is the first case report of acne fulminans in a patient with ulcerative colitis. It is noteworthy that the addition of diaminodiphenylsulfone was effective for treating the relapse of acne fulminans in this case. Copyright © 2011 S. Karger AG, Basel.

  1. Influence of preconsolidation on consolidation quality after stamp forming of C/PEEK composites

    Science.gov (United States)

    Slange, T. K.; Warnet, L.; Grouve, W. J. B.; Akkerman, R.

    2016-10-01

    Stamp forming is a rapid manufacturing technology used to shape flat blanks of thermoplastic composite material into three-dimensional components. Currently, expensive autoclave and press consolidation are used to preconsolidate blanks. This study investigates the influence of preconsolidation on final consolidation quality after stamp forming and explores the potential of alternative blank manufacturing methods that could reduce part costs. Blanks were manufactured using various blank manufacturing methods and subsequently were stamp formed. The consolidation quality both before and after stamp forming was compared, where the focus was on void content as the main measure for consolidation quality. The void content was characterized through thickness and density measurements, as well as by microscopy analysis. Results indicate that preconsolidation quality does have an influence on the final consolidation quality. This is due to the severe deconsolidation and limited reconsolidation during stamp forming. Nevertheless, the potential of automated fiber placement and ultrasonic spot welding as alternative blank manufacturing methods was demonstrated.

  2. Halloysite Nanotubes for Cleaning, Consolidation and Protection.

    Science.gov (United States)

    Cavallaro, Giuseppe; Lazzara, Giuseppe; Milioto, Stefana; Parisi, Filippo

    2018-01-10

    Herein, we report our recent research concerning the development of halloysite based protocols for cleaning, consolidation and protection purposes. Surface modification of halloysite cavity by anionic surfactants was explored to fabricate inorganic micelles able to solubilize hydrophobic contaminants. Hybrid dispersions based on halloysite and ecocompatible polymers were tested as consolidants for paper and waterlogged archaeological woods. Encapsulation of deacidifying and flame retardant agents within the halloysite lumen was conducted with aim to obtain nanofiller with a long-term protection ability. The results prove the suitability and versatility of halloysite nanotubes, which are perspective inorganic nanoparticles within materials science, remedation and conservation of cultural heritage fields. © 2018 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Effective elasticity coefficients of native rocks and consolidated granular matter

    International Nuclear Information System (INIS)

    Schulz, Beatrix M.; Schulz, Michael

    2008-01-01

    The elastic coefficients of binary heterogeneous materials, such as several native rock materials or consolidated granular matter will be determined in terms of a perturbation expansion. Furthermore, in order to check the validity of the obtained results, these are compared with numerical investigations using Boole's model of randomly distributed spheres. Finally, we apply the results on several classes of native rocks and consolidated granular materials

  4. Medial prefrontal-hippocampal connectivity and motor memory consolidation in depression and schizophrenia

    NARCIS (Netherlands)

    Genzel, L.K.E.; Dresler, M.; Cornu, M.; Jager, E.; Konrad, B.; Adamczyk, M.; Friess, E.; Steiger, A.; Czisch, M.; Goya-Maldonado, R.

    2015-01-01

    BACKGROUND: Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology. METHODS: We

  5. Consolidation of Similarity Knowledge via Pythagorean Theorem: A Turkish Case Study

    Science.gov (United States)

    Güler, Hatice Kübra; Arslan, Çigdem

    2017-01-01

    Understanding how students learn is important for both researchers and teachers. In terms of mathematics, constructing a new mathematical structure depends on conceptual understanding and connection with previous construct and they needs to be consolidated. A construct can be consolidated when the construct is recognized and used in the further…

  6. 7 CFR 4290.470 - Prior approval of merger, consolidation, or reorganization of RBIC.

    Science.gov (United States)

    2010-01-01

    ... merge, consolidate, change form of organization (corporation, limited liability company, or limited partnership) or reorganize without the Secretary's prior written approval. Any such merger, consolidation, or...

  7. Adenocarcinoma of the lung with scattered consolidation: radiological-pathological correlation and prognosis.

    Science.gov (United States)

    Jiang, Binghu; Takashima, Shodayu; Hakucho, Tomoaki; Hodaka, Numasaki; Yasuhiko, Tomita; Masahiko, Higashiyama

    2013-10-01

    To investigate the clinicopathological features and prognosis in patients with adenocarcinoma of the lung with scattered consolidation (ALSC). Between January 2006 and March 2010, 139 consecutive patients with lung adenocarcinoma of ≤3 cm, who underwent pulmonary resection for lung cancer, were investigated retrospectively. Radiologic classification was based on the findings of thin-section CT such as the presence of consolidation or ground-glass opacity (GGO). Type I (n=15) and Type II (n=14), showed a pure GGO and a mixed GGO with consolidation <50%, respectively. Type IV (n=38) and Type V (n=52) showed a mixed GGO with consolidation ≥50% and a pure consolidation, respectively. Type III (n=20) was the adenocarcinoma of the lung with scattered consolidation (ALSC). The clinicopathological features and prognosis of ALSC was investigated with comparative analysis and survival analysis. Because of the similar recurrence rate for Type I and Type II (P=1.000), Type IV and Type V (P=0.343), we merged Type I and Type II as Type I+II, Type IV and Type V as Type IV+V, respectively. In the 20 (14.4%) patients with ALSC, lymph node metastasis was not observed, and it was rare in lymphatic invasion and vascular invasion. On the basis of IASLC/ATS/ERS 2011 classification, 80% of the ALSC were preinvasive lesions. In Noguchi classification, there was no significant difference between Type I+II and ALSC (P=0.260). The prognosis of ALSC was similar to Type I+II (P=0.408), but better than Type IV+V (P=0.040). Adenocarcinoma of the lung with scattered consolidation (ALSC) on thin-section CT was a relatively favorable prognostic factor. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Modelling and simulation of the consolidation behavior during thermoplastic prepreg composites forming process

    Science.gov (United States)

    Xiong, H.; Hamila, N.; Boisse, P.

    2017-10-01

    Pre-impregnated thermoplastic composites have recently attached increasing interest in the automotive industry for their excellent mechanical properties and their rapid cycle manufacturing process, modelling and numerical simulations of forming processes for composites parts with complex geometry is necessary to predict and optimize manufacturing practices, especially for the consolidation effects. A viscoelastic relaxation model is proposed to characterize the consolidation behavior of thermoplastic prepregs based on compaction tests with a range of temperatures. The intimate contact model is employed to predict the evolution of the consolidation which permits the microstructure prediction of void presented through the prepreg. Within a hyperelastic framework, several simulation tests are launched by combining a new developed solid shell finite element and the consolidation models.

  9. Methodology of Prioritization of Land Consolidation and Land Exchange Interventions

    Science.gov (United States)

    Len, Przemyslaw

    2017-12-01

    Land consolidation is one of the basic development activities in rural areas intended to comprehensively improve the organization of agricultural production space. Merging and exchange of parcels are aimed at transforming a fragmented and “checkerboarded” landscape containing excessively long fields into plots as large and regular as possible. Land consolidation decisions are based on detailed analyses of relevant parameters. Properly carried out land consolidation creates an opportunity to organize agricultural holdings in an appropriate way, and, at the same time, to preserve the natural environment. Consolidation provides appropriate conditions for sustainable and multi-functional rural development by limiting the harmful influence of intensive agriculture on the natural environment. It also leads to an improvement in living and working conditions for inhabitants of rural areas. The analysis conducted in this study was aimed at singling out villages in the commune of Paradyż in which consolidation of arable land was required most urgently. Factors describing the investigated villages were selected on the basis of a comprehensive analysis of the natural, social, economic and financial conditions found in those localities. The analysis was conducted using data obtained from the Land and Property Register of the District Office in Opoczno and data from the Office of the Commune of Paradyż. The study allowed us to determine which areas required land consolidation and exchange interventions, thus becoming a basis for applying for financial resources necessary to reach the aforementioned goal. A special role in empirical studies, especially comparative studies, of human activity is played by taxonomic methods, which involve linear ordering of items according to a synthetic indicator characterizing those items, which is calculated on the basis of a set of shared features. These methods are widely used in econometrics and socio-economic research to create all

  10. Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma

    Science.gov (United States)

    Chen, Yi-Dan; Liang, Zhong-Yuan; Cen, Yan-Yan; Zhang, He; Han, Mei-Gui; Tian, Yun-Qiao; Zhang, Jie; Li, Shu-Jun; Yang, Da-Sheng

    2015-01-01

    The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics. PMID:26640367

  11. Land Reform and Land Consolidation in Central and Eastern Europe after 1989

    DEFF Research Database (Denmark)

    Hartvigsen, Morten B.

    instruments are well on the way in the region, land banking instruments have largely failed in the region, at least as tools for supporting land consolidation programs. Based on the limited theory available, the analysis has revealed how limited land mobility is often hampering the outcome of land...... are not competitive in the globalized economy. Drawing on the classical theory on land fragmentation, this PhD study explores the coherence between the land reform approaches applied in 25 study countries and the outcome in form of farm structures and land fragmentation. Most of the Central and Eastern European...... countries have introduced land consolidation instruments to address the structural problems in agriculture. The PhD study analyses the experiences from introduction of land consolidation and land banking instruments and provides the first full overview of the experiences achieved. While land consolidation...

  12. Malawi's Traditional Leadership and Democracy Consolidation ...

    African Journals Online (AJOL)

    is that the tendency to brand traditional leadership as undemocratic masks debate on its great potential for the promotion of democracy. The article contends that efforts towards democracy consolidation require foregoing harmonious power relations and linkages between traditional leaders and elected local governments; ...

  13. Experimental Studies on Earthen Architecture Sites Consolidated with BS Materials in Arid Regions

    Directory of Open Access Journals (Sweden)

    Dong Zhao

    2016-01-01

    Full Text Available This paper takes the preservation works on the archaeological sites of Gaochang Ruins, Xinjiang, as background. Based on the soil characteristics analysis on the archaeological sites, experimental studies were conducted on the consolidation effect of the BS-10 consolidation material on the archaeological sites of adobe and rammed earth. The results showed the following:, after consolidation, the wind erosion resistance of the soil on the archaeological sites was substantially increased, and the wind erosion modulus was reduced by 5~8 times; the soil exhibited fine grid structure and significantly reduced degree of permeability, while still maintaining the moisture exchange between inside and outside the soil; there is excellent ageing resistance; the resistance to freezing and thawing was closely related to the soil water content and had little influence in arid regions; the water resistance was improved and could satisfy the requirements for consolidating the sites in arid regions; the unconfined compressive strength was improved moderately, which was the key direction of improvement in the future, and the consolidated soil did not form duricrust on the surface and had good bonding strength with the internal parts. The BS-10 material can meet the consolidation requirements for the earthen archaeological sites in arid regions of northwest China.

  14. An analysis on the contribution of civil society to democratic consolidation in Turkey

    OpenAIRE

    Torus, Emre

    2007-01-01

    Cataloged from PDF version of article. This is an analysis on the contribution of civil society to democratic consolidation in Turkey. This thesis will try to understand this problematic by assessing the civil society’s formal structure, legal framework, internal values and its impact during the consolidation process. The key aim here is to understand the civil society’s role as a contributor to democratic consolidation by mapping the civil society and democratic consolidati...

  15. An investigation into the development of consolidation of distributed generation within the wholesale electricity trading arrangements

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    In this report the problems faced by distributed generators is explored under the New Electricity Trading Arrangements (NETA) in relation to the low price received for generation above contract requirement and the high price charged for under generation, and the lack of an alternative to the bilateral contract. The background to the study is traced, and the economics and history of consolidation, the NETA environment, development of imbalance prices, and the market for consolidation are outlined. An overview of consolidation in practice is presented, covering the generators and suppliers views, and specialist consolidators. The main options for development, and consolidation models are considered as well as net benefits, regulatory and commercial impediments to consolidation, and the potential impact of BETA.

  16. An investigation into the development of consolidation of distributed generation within the wholesale electricity trading arrangements

    International Nuclear Information System (INIS)

    2005-01-01

    In this report the problems faced by distributed generators is explored under the New Electricity Trading Arrangements (NETA) in relation to the low price received for generation above contract requirement and the high price charged for under generation, and the lack of an alternative to the bilateral contract. The background to the study is traced, and the economics and history of consolidation, the NETA environment, development of imbalance prices, and the market for consolidation are outlined. An overview of consolidation in practice is presented, covering the generators and suppliers views, and specialist consolidators. The main options for development, and consolidation models are considered as well as net benefits, regulatory and commercial impediments to consolidation, and the potential impact of BETA

  17. UbuntuNet Alliance : Consolidating Research and Education ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    UbuntuNet Alliance : Consolidating Research and Education Networking - Phase II ... North of Sahara, South of Sahara, United States ... social science, population and public health, and health systems research relevant to the emerging crisis.

  18. New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

    Science.gov (United States)

    Levy, Roi; Levitan, David; Susswein, Abraham J

    2016-01-01

    Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory. DOI: http://dx.doi.org/10.7554/eLife.17769.001 PMID:27919318

  19. New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process.

    Science.gov (United States)

    Levy, Roi; Levitan, David; Susswein, Abraham J

    2016-12-06

    Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory.

  20. Consolidating African Research and Education Networking ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Consolidating African Research and Education Networking (CORENA) - Phase I. African universities and research institutions possess significant human capacity, but their contribution to national human development as well as their intellectual property output is still very limited. A major cause of this is lack of easy and ...

  1. Status of the consolidation of the LHC superconducting magnets and circuits

    International Nuclear Information System (INIS)

    Tock, J Ph; Atieh, S; Bodart, D; Bordry, F; Bourcey, N; Cruikshank, P; Dahlerup-Petersen, K; Dalin, J M; Garion, C; Musso, A; Ostojic, R; Perin, A; Pojer, M; Savary, F; Scheuerlein, C

    2014-01-01

    The first LHC long shutdown (LS1) started in February 2013. It was triggered by the need to consolidate the 13 kA splices between the superconducting magnets to allow the LHC to reach safely its design energy of 14 TeV center of mass. The final design of the consolidated splices is recalled. 1695 interconnections containing 10 170 splices have to be opened. In addition to the work on the 13 kA splices, the other interventions performed during the first long shut-down on all the superconducting circuits are described. All this work has been structured in a project, gathering about 280 persons. The opening of the interconnections started in April 2013 and consolidation works are planned to be completed by August 2014. This paper describes first the preparation phase with the building of the teams and the detailed planning of the operation. Then, it gives feedback from the worksite, namely lessons learnt and adaptations that were implemented, both from the technical and organizational points of view. Finally, perspectives for the completion of this consolidation campaign are given.

  2. Status of the Consolidation of the LHC Superconducting Magnets and Circuits

    Science.gov (United States)

    Tock, J. Ph; Atieh, S.; Bodart, D.; Bordry, F.; Bourcey, N.; Cruikshank, P.; Dahlerup-Petersen, K.; Dalin, J. M.; Garion, C.; Musso, A.; Ostojic, R.; Perin, A.; Pojer, M.; Savary, F.; Scheuerlein, C.

    2014-05-01

    The first LHC long shutdown (LS1) started in February 2013. It was triggered by the need to consolidate the 13 kA splices between the superconducting magnets to allow the LHC to reach safely its design energy of 14 TeV center of mass. The final design of the consolidated splices is recalled. 1695 interconnections containing 10 170 splices have to be opened. In addition to the work on the 13 kA splices, the other interventions performed during the first long shut-down on all the superconducting circuits are described. All this work has been structured in a project, gathering about 280 persons. The opening of the interconnections started in April 2013 and consolidation works are planned to be completed by August 2014. This paper describes first the preparation phase with the building of the teams and the detailed planning of the operation. Then, it gives feedback from the worksite, namely lessons learnt and adaptations that were implemented, both from the technical and organizational points of view. Finally, perspectives for the completion of this consolidation campaign are given.

  3. Interacting Brain Systems Modulate Memory Consolidation

    Science.gov (United States)

    McIntyre, Christa K.; McGaugh, James L.; Williams, Cedric L.

    2011-01-01

    Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders. PMID:22085800

  4. 7 CFR 1735.19 - Mergers and consolidations.

    Science.gov (United States)

    2010-01-01

    ... Basic Policies § 1735.19 Mergers and consolidations. RUS does not make loans for the sole purpose of... making loans to the telephone system to finance the improvement or extension of telephone service in...

  5. Coupling of Thalamocortical Sleep Oscillations Are Important for Memory Consolidation in Humans.

    Directory of Open Access Journals (Sweden)

    Mohammad Niknazar

    Full Text Available Sleep, specifically non-rapid eye movement (NREM sleep, is thought to play a critical role in the consolidation of recent memories. Two main oscillatory activities observed during NREM, cortical slow oscillations (SO, 0.5-1.0 Hz and thalamic spindles (12-15 Hz, have been shown to independently correlate with memory improvement. Yet, it is not known how these thalamocortical events interact, or the significance of this interaction, during the consolidation process. Here, we found that systemic administration of the GABAergic drug (zolpidem increased both the phase-amplitude coupling between SO and spindles, and verbal memory improvement in humans. These results suggest that thalamic spindles that occur during transitions to the cortical SO Up state are optimal for memory consolidation. Our study predicts that the timely interactions between cortical and thalamic events during consolidation, contribute to memory improvement and is mediated by the level of inhibitory neurotransmission.

  6. 78 FR 59791 - Annual Company-Run Stress Tests at Banking Organizations With Total Consolidated Assets of More...

    Science.gov (United States)

    2013-09-30

    ... bank on its Consolidated Financial Statements for Bank Holding Companies (FR Y-9C) or Consolidated... companies with $50 billion or more in total consolidated assets and any non-bank financial companies... with total consolidated assets of $50 billion or more and nonbank financial companies supervised by the...

  7. 78 FR 60695 - Regulatory Reorganization; Administrative Changes to Regulations Due to the Consolidation of the...

    Science.gov (United States)

    2013-10-02

    ... Consolidation of the Financial Management Service and the Bureau of the Public Debt Into the Bureau of the... Service''). The new bureau consolidated the bureaus formerly known as the Financial Management Service... Register on May 24, 2013. This consolidation requires reorganization of, and administrative changes to...

  8. Consolidity analysis for fully fuzzy functions, matrices, probability and statistics

    Directory of Open Access Journals (Sweden)

    Walaa Ibrahim Gabr

    2015-03-01

    Full Text Available The paper presents a comprehensive review of the know-how for developing the systems consolidity theory for modeling, analysis, optimization and design in fully fuzzy environment. The solving of systems consolidity theory included its development for handling new functions of different dimensionalities, fuzzy analytic geometry, fuzzy vector analysis, functions of fuzzy complex variables, ordinary differentiation of fuzzy functions and partial fraction of fuzzy polynomials. On the other hand, the handling of fuzzy matrices covered determinants of fuzzy matrices, the eigenvalues of fuzzy matrices, and solving least-squares fuzzy linear equations. The approach demonstrated to be also applicable in a systematic way in handling new fuzzy probabilistic and statistical problems. This included extending the conventional probabilistic and statistical analysis for handling fuzzy random data. Application also covered the consolidity of fuzzy optimization problems. Various numerical examples solved have demonstrated that the new consolidity concept is highly effective in solving in a compact form the propagation of fuzziness in linear, nonlinear, multivariable and dynamic problems with different types of complexities. Finally, it is demonstrated that the implementation of the suggested fuzzy mathematics can be easily embedded within normal mathematics through building special fuzzy functions library inside the computational Matlab Toolbox or using other similar software languages.

  9. Transvaal Consolidated Land and Exploration Company, Limited

    International Nuclear Information System (INIS)

    Lawrence, R.S.

    1983-01-01

    The difficult economic circumstances with which almost the whole world had to contend, brought serious financial crisis in many countries. South Africa also had its own share of serious problems. Despite this situation, Transvaal Consolidated Land and Exploration Company, Limited, showed on increase in earnings of 24 per cent per share. The reason for this lies mainly in two areas. Firstly the company acquired the mining related business of Rand Mines, Limited. Included in the acquisition was a partfolio of shares mainly in the company's associated gold and uranium mining companies and additional shares in its listed coal mining subsidiaries. Secondly, the average gold price realised by producers in rand terms, was considerably higher than in the previous year. Consolidated profit attributable to members increased by 52 per cent to R82,6 million

  10. Local Identity in Times of Jurisdictional Consolidation

    DEFF Research Database (Denmark)

    Hansen, Sune Welling; Kjær, Ulrik

    of a dataset which consists of large scale citizen surveys conducted in 2001, 2009 and 2013, combined with register data on the Danish municipalities (the two surveys in 2001 and 2009 even have a panel structure). Our paper contributes to the existing literature on local identity by examining the influence......Reforming the public sector has become increasingly popular. Some of the reforms have been jurisdictional consolidations of subnational authorities such as regions and municipalities. One question which remains unanswered is whether such consolidations affect citizens’ local identity? We take...... a first step towards providing an answer by examining whether citizens’ affective attachment to their municipality – and other administrative and geographical areas – declined or flourished in connection with a large-scale municipal reform implemented in Denmark in 2007. Empirically, we make use...

  11. Prospective Evaluation of Quality of Life and Neurocognitive Effects in Patients With Multiple Brain Metastases Receiving Whole-Brain Radiotherapy With or Without Thalidomide on Radiation Therapy Oncology Group (RTOG) Trial 0118

    International Nuclear Information System (INIS)

    Corn, Benjamin W.; Moughan, Jennifer M.S.; Knisely, Jonathan P.S.; Fox, Sherry W.; Chakravarti, Arnab; Yung, W.K. Alfred; Curran, Walter J.; Robins, H. Ian; Brachman, David G.; Henderson, Randal H.; Mehta, Minesh P.; Movsas, Benjamin

    2008-01-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) ± thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. Methods and Materials: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. Results: Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. Conclusions: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population

  12. Reduced susceptibility to interference in the consolidation of motor memory before adolescence.

    Directory of Open Access Journals (Sweden)

    Shoshi Dorfberger

    2007-02-01

    Full Text Available Are children superior to adults in consolidating procedural memory? This notion has been tied to "critical," early life periods of increased brain plasticity. Here, using a motor sequence learning task, we show, in experiment 1, that a the rate of learning during a training session, b the gains accrued, without additional practice, within a 24 hours post-training interval (delayed consolidation gains, and c the long-term retention of these gains, were as effective in 9, 12 and 17-year-olds and comparable to those reported for adults. However, a follow-up experiment showed that the establishment of a memory trace for the trained sequence of movements was significantly more susceptible to interference by a subsequent motor learning experience (practicing a reversed movement sequence in the 17-year-olds compared to the 9 and 12-year-olds. Unlike the 17-year-olds, the younger age-groups showed significant delayed gains even after interference training. Altogether, our results indicate the existence of an effective consolidation phase in motor learning both before and after adolescence, with no childhood advantage in the learning or retention of a motor skill. However, the ability to co-consolidate different, successive motor experiences, demonstrated in both the 9 and 12-year-olds, diminishes after puberty, suggesting that a more selective memory consolidation process takes over from the childhood one. Only the adult consolidation process is gated by a recency effect, and in situations of multiple, clashing, experiences occurring within a short time-interval, adults may less effectively establish in memory experiences superseded by newer ones.

  13. Investigation of fiber-reinforced self-consolidating concrete.

    Science.gov (United States)

    2010-05-01

    The rising cost of materials and labor, as well as the demand for faster construction, has prompted development of cheaper, faster alternatives to conventional building techniques. Self-consolidating concrete (SCC), a high performance concrete charac...

  14. Non-Interfering Effects of Active Post-Encoding Tasks on Episodic Memory Consolidation in Humans.

    Science.gov (United States)

    Varma, Samarth; Takashima, Atsuko; Krewinkel, Sander; van Kooten, Maaike; Fu, Lily; Medendorp, W Pieter; Kessels, Roy P C; Daselaar, Sander M

    2017-01-01

    So far, studies that investigated interference effects of post-learning processes on episodic memory consolidation in humans have used tasks involving only complex and meaningful information. Such tasks require reallocation of general or encoding-specific resources away from consolidation-relevant activities. The possibility that interference can be elicited using a task that heavily taxes our limited brain resources, but has low semantic and hippocampal related long-term memory processing demands, has never been tested. We address this question by investigating whether consolidation could persist in parallel with an active, encoding-irrelevant, minimally semantic task, regardless of its high resource demands for cognitive processing. We distinguish the impact of such a task on consolidation based on whether it engages resources that are: (1) general/executive, or (2) specific/overlapping with the encoding modality. Our experiments compared subsequent memory performance across two post-encoding consolidation periods: quiet wakeful rest and a cognitively demanding n-Back task. Across six different experiments (total N = 176), we carefully manipulated the design of the n-Back task to target general or specific resources engaged in the ongoing consolidation process. In contrast to previous studies that employed interference tasks involving conceptual stimuli and complex processing demands, we did not find any differences between n-Back and rest conditions on memory performance at delayed test, using both recall and recognition tests. Our results indicate that: (1) quiet, wakeful rest is not a necessary prerequisite for episodic memory consolidation; and (2) post-encoding cognitive engagement does not interfere with memory consolidation when task-performance has minimal semantic and hippocampally-based episodic memory processing demands. We discuss our findings with reference to resource and reactivation-led interference theories.

  15. The Demonstration of Short-Term Consolidation.

    Science.gov (United States)

    Jolicoeur, Pierre; Dell'Acqua, Roberto

    1998-01-01

    Results of seven experiments involving 112 college students or staff using a dual-task approach provide evidence that encoding information into short-term memory involves a distinct process termed short-term consolidation (STC). Results suggest that STC has limited capacity and that it requires central processing mechanisms. (SLD)

  16. 26 CFR 1.818-8 - Special rules relating to consolidated returns and certain capital losses.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Special rules relating to consolidated returns... Special rules relating to consolidated returns and certain capital losses. Section 818(g) provides that, in the case of a life insurance company filing or required to file a consolidated return under...

  17. Consolidation theory and its applicability to the dewatering and covering of uranium-mill tailings

    International Nuclear Information System (INIS)

    Gates, T.E.

    1982-11-01

    This report is a review and evaluation of soil consolidation theories applicable for evaluating settlement during dewatering and subsequent covering of uranium-mill tailings. Such theories may be used to predict both consolidation and water flow related effects in uranium-mill tailings during drainage, following sluicing into burial pits. A consolidation theory to be useful must consider the effect of time-dependent loads, nonhomogeneous soil mass, nonlinear variation of soil properties with the stress-state parameters, large strain, and saturated and unsaturated flow. Constitutive relations linking the stress-deformation-state variables with void ratio should be adopted for predicting both consolidation and fluid-flow interaction in unsaturated uranium-mill tailings

  18. Tax system of consolidated taxpayers groups in Russia and ways of its improvement

    Directory of Open Access Journals (Sweden)

    Leontieva Jamila

    2018-01-01

    Full Text Available One of perspective directions of business development is creation of large companies (holdings, concerns, corporations, etc. that unite legally separate economic entities linked by organizational, economic and civil-law subordination. Increasing the efficiency of such companies and, on this basis, the growth of the national economy and its competitiveness in the world market is influenced by tax system of a group of interconnected companies. International experience has shown that these tax systems in different countries were created under the influence of a combination of various factors, most of which were due to both, historical development and mutual influence. The article presents the development of methodological approach to the improvement of Russian tax system for consolidated groups of taxpayers, which requires the integration of a number of scientific ideas and hypotheses of various schools and international experience in formation and development of the institution of consolidated tax reporting. This approach is based on the fact that consolidated group of taxpayers should be considered as an economic entity, which is a separate object of financial accounting and tax system. In present work with the help of such general scientific methods as system approach, comparison, method of data systematization and generalization, the conditions for creating consolidated group of taxpayers were studied; mechanism of consolidation and system of consolidated profitability reporting for the group of companies, their main content; the procedure for granting the right to set off losses, including losses incurred for the period preceding the year of consolidation of one company member of the group, against the profits of other members of the group.

  19. Characterization and modeling of sediment settling, consolidation, and suspension to optimize coastal Louisiana restoration

    Science.gov (United States)

    Sha, X.; Xu, K.; Bentley, S. J.; Robichaux, P. A.

    2018-04-01

    Many research efforts have been undertaken over many decades in the field of Louisiana coastal restoration, but long-term experiments for sediment suspension and consolidation in diversion-receiving basins are still limited, despite significance of this topic to ongoing restoration strategies. Sediment samples were collected from two active diversions on the Mississippi River: West Bay, a semi-enclosed bay located on the Mississippi River Delta and fed by the West Bay Diversion, and from Big Mar pond, a receiving basin of the Caernarvon freshwater diversion from the lower Mississippi River, Louisiana, USA. A dual-core Gust Erosion Microcosm System was used to measure time-series (0.5, 1, 2, 3, 4, 5, and 6-months after initial settling) erodibility at seven shear stress regimes (0.01-0.60 Pa) using experimental cores prepared with two initial sediment concentrations (60 and 120 kg m-3). A 230-cm tall settling column with nine sampling ports was used to measure the consolidation rates for initial sediment concentrations ranging from fluid mud (10 kg m-3) to dredge effluent (120 kg m-3), in combination with two levels of salinity (1 and 5). The erodibility of West Bay sediment decreased with increasing time of consolidation. The critical shear stress for resuspension increased from 0.2 Pa after 2 months to 0.45 Pa after 4 months of consolidation. The consolidation rates were inversely and exponentially related to initial sediment concentrations. Consolidation tests in salinity of 1 generally settled faster than that in salinity of 5, and consolidation tests with low sediment concentration tests generally settled faster than high-concentration tests. An exponential coefficient was added in the Sanford (2008) model to better predict the consolidation profile of both rapid early settling and slow self-weight consolidation processes. Our study suggests that enclosed basin, low salinity, relatively low sediment concentration and minimized disturbance for 4 months all favor

  20. Consolidating Orientation of Pedagogic Functions of University Teachers in International Students Training

    Science.gov (United States)

    Dzhamalova, Bika B.; Timonin, Andrey I.; Kolesov, Vladimir I.; Pavlov, Vladimir V.; Evstegneeva, Anastasiia A.

    2016-01-01

    This article is focused on the development of the structure and content of consolidating orientation of pedagogical functions of university teachers in international students' training. The leading method of research is the modeling method that allows producing of the established structure's and content's justification of consolidating orientation…